Trispecific and/or trivalent binding proteins for prevention or treatment of hiv infection

Abstract

Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, where in a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.

What is claimed is: 
     
         1 . A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I];
   a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1   [II];
 
   a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1   [III],
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV];
 
   wherein   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is an immunoglobulin C H1  heavy chain constant domain; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.   
     
     
         2 . A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I]
   and a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1 -hinge-C H2 -C H3   [II]
 
   and a third polypeptide chain comprises a structure represented by the formula: 
   V H3 -C H1 -hinge-C H2 -C H3   [III]
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV]
 
   wherein:   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is an immunoglobulin C H1  heavy chain constant domain;   C H2  is an immunoglobulin C H2  heavy chain constant domain;   C H3  is an immunoglobulin C H3  heavy chain constant domain;   hinge is an immunoglobulin hinge region connecting the C H1  and C H2  domains; and   L 1 , L 2 , L 3  and L 4  are amino acid linkers;   and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.   
     
     
         3 . The binding protein of  claim 1  or  claim 2 , wherein the one or more HIV target protein is selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 160. 
     
     
         4 . The binding protein of  claim 1  or  claim 2 , wherein the binding protein is trispecific and capable of specifically binding three different epitopes on a single HIV target protein. 
     
     
         5 . The binding protein of  claim 1  or  claim 2 , wherein the binding protein is trispecific and capable of specifically binding two different epitopes on a first HIV target protein, and one epitope on a second HIV target protein, wherein the first and second HIV target proteins are different. 
     
     
         6 . The binding protein of  claim 1  or  claim 2 , wherein the binding protein is trispecific and capable of specifically binding three different antigen targets. 
     
     
         7 . The binding protein of  claim 1  or  claim 2 , wherein the binding protein is capable of inhibiting the function of one or more HIV target proteins. 
     
     
         8 . The binding protein of any one of  claims 1 - 7 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively. 
     
     
         9 . The binding protein of any one of  claims 1 - 7 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         10 . The binding protein of any one of  claims 1 - 9 , wherein V L1  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         11 . The binding protein of any one of  claims 1 - 10 , wherein V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively. 
     
     
         12 . The binding protein of any one of  claims 1 - 10 , wherein V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         13 . The binding protein of any one of  claims 1 - 12 , wherein V L2  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         14 . The binding protein of any one of  claims 1 - 13 , wherein V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; or a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively. 
     
     
         15 . The binding protein of any one of  claims 1 - 13 , wherein V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         16 . The binding protein of any one of  claims 1 - 15 , wherein V L3  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, and 521. 
     
     
         17 . The binding protein of any one of  claims 1 - 16 , wherein V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively. 
     
     
         18 . The binding protein of any one of  claims 1 - 16 , wherein V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         19 . The binding protein of any one of  claims 1 - 18 , wherein V H1  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         20 . The binding protein of any one of  claims 1 - 19 , wherein V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively. 
     
     
         21 . The binding protein of any one of  claims 1 - 19 , wherein V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         22 . The binding protein of any one of  claims 1 - 21 , wherein V H2  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         23 . The binding protein of any one of  claims 1 - 22 , wherein V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; or a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively. 
     
     
         24 . The binding protein of any one of  claims 1 - 22 , wherein V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         25 . The binding protein of any one of  claims 1 - 24 , wherein V H3  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, and 508. 
     
     
         26 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V L2  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V L3  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 266, a CDR-L2 comprising the sequence of SEQ ID NO: 267, and a CDR-L3 comprising the sequence of SEQ ID NO: 268; V H1  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V H2  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V H3  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 248, a CDR-H2 comprising the sequence of SEQ ID NO: 497, and a CDR-H3 comprising the sequence of SEQ ID NO: 250. 
     
     
         27 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 512, V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 502. 
     
     
         28 . The binding protein of any one of  claims 1 - 27 , wherein V L1  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V L2  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V L3  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 512; V H1  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V H2  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V H3  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 502. 
     
     
         29 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V L2  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V L3  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V H1  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; V H2  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V H3  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253. 
     
     
         30 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; and V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503. 
     
     
         31 . The binding protein of any one of  claims 1 - 25  and  29 - 30 , wherein V L1  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V L2  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V L3  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V H1  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; V H2  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; and V H3  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503. 
     
     
         32 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277; V L2  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 500, a CDR-L2 comprising the sequence of SEQ ID NO: 501, and a CDR-L3 comprising the sequence of SEQ ID NO: 274; V L3  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V H1  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; V H2  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 254, a CDR-H2 comprising the sequence of SEQ ID NO: 255, and a CDR-H3 comprising the sequence of SEQ ID NO: 256; and V H3  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253. 
     
     
         33 . The binding protein of any one of  claims 1 - 25 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 519; V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 518; V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 506; V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 504; and V H 3 comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503. 
     
     
         34 . The binding protein of any one of  claims 1 - 25  and  32 - 33 , wherein V L1  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519; V L2  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518; V L3  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513, V H1  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506; V H2  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; and V H3  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503. 
     
     
         35 . The binding protein of  claim 1 , wherein the second polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         36 . The binding protein of  claim 1 , wherein the third polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         37 . The binding protein of  claim 1 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         38 . The binding protein of  claim 1 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         39 . The binding protein of  claim 1 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H1  immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         40 . The binding protein of  claim 2 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         41 . The binding protein of  claim 2 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         42 . The binding protein of  claim 2 , wherein the C H3  domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         43 . The binding protein of  claim 1  or  claim 2 , wherein at least one of L 1 , L 2 , L 3 , or L 4  is independently 0 amino acids in length. 
     
     
         44 . The binding protein of  claim 1  or  claim 2 , wherein L 1 , L 2 , L 3 , or L 4  are each independently at least one amino acid in length. 
     
     
         45 . The binding protein of any one of  claims 1 - 44 , wherein L 1  comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525). 
     
     
         46 . A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I]
   and a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1   [II]
 
   and a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1   [III]
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV]
 
   wherein:   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is the immunoglobulin C H1  heavy chain constant domain; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;   wherein:
 (a) V L1 , V L2  and V L3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or 
 (b) V L1 , V L2  and V L3  each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and 
   wherein:
 (a) V H1 , V H2 , and V H3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or 
 (b) V H1 , V H2 , and V H3  each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265. 
   
     
     
         47 . A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I]
   
       and a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1 -hinge-C H2 -C H3   [II]
 
 and a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1 -hinge-C H2 -C H3   [III]
 
 
 and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV]
 
 
 wherein: 
 V L1  is a first immunoglobulin light chain variable domain; 
 V L2  is a second immunoglobulin light chain variable domain; 
 V L3  is a third immunoglobulin light chain variable domain; 
 V H1  is a first immunoglobulin heavy chain variable domain; 
 V H2  is a second immunoglobulin heavy chain variable domain; 
 V H3  is a third immunoglobulin heavy chain variable domain; 
 C L  is an immunoglobulin light chain constant domain; 
 C H1  is the immunoglobulin C H1  heavy chain constant domain; 
 C H2  is an immunoglobulin C H2  heavy chain constant domain; 
 C H3  is an immunoglobulin C H3  heavy chain constant domain; 
 hinge is an immunoglobulin hinge region connecting the C H1  and C H2  domains; and 
 L 1 , L 2 , L 3 , and L 4  are amino acid linkers; 
 wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; 
 wherein:
 (a) V L1 , V L2  and V L3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 2, 4, 10, 12, 18, 20, 26, 28, 34, 36, 42, 44, 50, 52, 58, 60, 66, 68, 74, 76, 82, 84, 90, 92, 98, 100, 106, 108, 114, 116, 122, 124, 130, 132, 138, 140, 146, 148, 154, 156, 162, 164, 170, 172, 178, 180, 186, 188, 194, 196, 202, 204, 210, 212, 218, 220, 226, 228, 233, 235, 241, 243; or 
 (b) V L1 , V L2  and V L3  each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs:266-283; and 
 
 wherein:
 (a) V H1 , V H2 , and V H3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 1, 3, 9, 11, 17, 10, 25, 27, 33, 35, 41, 43, 49, 51, 57, 59, 65, 67, 73, 75, 81, 83, 89, 91, 97, 99, 105, 107, 113, 115, 121, 123, 129, 131, 137, 139, 145, 147, 153, 155, 161, 163, 169, 171, 177, 179, 185, 187, 193, 195, 201, 203, 209, 211, 217, 219, 225, 227, 232, 234, 240, 242; or 
 (b) V H1 , V H2 , and V H3  each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-265. 
 
 
     
     
         48 . The binding protein of  claim 46 , wherein the second polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         49 . The binding protein of  claim 46 , wherein the third polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         50 . The binding protein of  claim 46 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         51 . The binding protein of  claim 46 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         52 . The binding protein of  claim 46 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         53 . The binding protein of  claim 47 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         54 . The binding protein of  claim 47 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         55 . The binding protein of  claim 47 , wherein the C H3  domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         56 . The binding protein of  claim 46  or  claim 47 , wherein at least one of L 1 , L 2 , L 3 , or L 4  is independently 0 amino acids in length. 
     
     
         57 . The binding protein of  claim 46  or  claim 47 , wherein L 1 , L 2 , L 3 , or L 4  are each independently at least one amino acid in length. 
     
     
         58 . The binding protein of any one of  claims 46 - 57 , wherein L 1  comprises Asp-Lys-Thr-His-Thr (SEQ ID NO: 525). 
     
     
         59 . A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein:
 (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2;   (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 9; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10;   (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 20; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 19; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 18;   (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 28 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 28; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 27 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 27; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 25 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 25; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 26 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 26;   (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 36 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 35 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 33 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 34 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34;   (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 44; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 43 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 43; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 41 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 41; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 42 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 42;   (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 52 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 52; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 51 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 49 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 49; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 50 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 50;   (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 60 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 60; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 59 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 59; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 57 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 57; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 58 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 58;   (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66;   (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74;   (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 84; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82;   (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:92; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90;   (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98;   (n) the first polypeptide comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106;   (o) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114;   (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122;   (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130;   (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138;   (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146;   (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154;   (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 163; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162;   (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170;   (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 180 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 180; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 179 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 179; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 177 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 177; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 178 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 178;   (x) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 188 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 188; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 187 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 187; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 185 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 185; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 186 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 186;   (y) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 196 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 196; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 195 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 195; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 193 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 193; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 194 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 194;   (z) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 204 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 204; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 203 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 203; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 201 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 202 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202;   (aa) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 212; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 211 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 211; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 209 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 209; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 210 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 210;   (bb) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 220 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 219 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 219; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 217 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 217; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 218 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 218;   (cc) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 228 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 228; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 227 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 227; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 225 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 225; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 226 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 226;   (dd) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 235 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 234 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 234; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 232 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 232; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 233 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 233; or   (ee) first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 243 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 243; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 242 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 242; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 240 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 240; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 241 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 241.   
     
     
         60 . A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I];
   a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1   [II];
 
   a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1   [III];
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV];
 
   wherein   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is the immunoglobulin C H1  heavy chain constant domain; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.   
     
     
         61 . A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins and one or more T cell target proteins, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I];
   a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1 -hinge-C H2 -C H3   [II];
 
   a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1 -hinge-C H2 -C H3   [III];
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV];
 
   wherein   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is the immunoglobulin C H1  heavy chain constant domain;   C H2  is an immunoglobulin C H2  heavy chain constant domain;   C H3  is an immunoglobulin C H3  heavy chain constant domain;   hinge is an immunoglobulin hinge region connecting the C H1  and C H2  domains; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair.   
     
     
         62 . The binding protein of  claim 60  or  claim 61 , wherein the one or more HIV target proteins are selected from the group consisting of glycoprotein 120, glycoprotein 41 and glycoprotein 160. 
     
     
         63 . The binding protein of  claim 60  or  claim 61 , wherein the one or more T cell target proteins are CD3 or CD28. 
     
     
         64 . The binding protein of  claim 60  or  claim 61 , wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different epitopes on a single T cell target protein. 
     
     
         65 . The binding protein of  claim 60  or  claim 61 , wherein the binding protein is trispecific and capable of specifically binding an HIV target protein and two different T cell target proteins. 
     
     
         66 . The binding protein of  claim 60  or  claim 61 , wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different epitopes on a single HIV target protein. 
     
     
         67 . The binding protein of  claim 60  or  claim 61 , wherein the binding protein is trispecific and capable of specifically binding a T cell target protein and two different HIV target proteins. 
     
     
         68 . The binding protein of  claim 60  or  claim 61 , wherein the first and second polypeptide chains form two antigen binding sites that specifically target two T cell target proteins, and the third and fourth polypeptide chains form an antigen binding site that specifically binds an HIV target protein. 
     
     
         69 . The binding protein of any one of  claims 60 - 68 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively. 
     
     
         70 . The binding protein of any one of  claims 60 - 68 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         71 . The binding protein of any one of  claims 60 - 70 , wherein V L1  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         72 . The binding protein of any one of  claims 60 - 71 , wherein V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively. 
     
     
         73 . The binding protein of any one of  claims 60 - 71 , wherein V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         74 . The binding protein of any one of  claims 60 - 73 , wherein V L2  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         75 . The binding protein of any one of  claims 60 - 74 , wherein V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 comprising a sequence as set forth in SEQ ID NOs: 266, 267, and 268, respectively; a sequence as set forth in SEQ ID NOs: 269, 270, and 271, respectively; a sequence as set forth in SEQ ID NOs: 500, 501, and 274, respectively; a sequence as set forth in SEQ ID NOs: 275, 276, and 277, respectively; a sequence as set forth in SEQ ID NOs: 281, 282, and 283, respectively; a sequence as set forth in SEQ ID NOs: 278, 279, and 280, respectively; a sequence as set forth in SEQ ID NOs: 488, 489, and 490, respectively; a sequence as set forth in SEQ ID NOs: 491, 492, and 493, respectively; or a sequence as set forth in SEQ ID NOs: 494, 495, and 496, respectively. 
     
     
         76 . The binding protein of any one of  claims 60 - 74 , wherein V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         77 . The binding protein of any one of  claims 60 - 76 , wherein V L3  comprises a light chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, and 524. 
     
     
         78 . The binding protein of any one of  claims 60 - 77 , wherein V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively. 
     
     
         79 . The binding protein of any one of  claims 60 - 77 , wherein V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         80 . The binding protein of any one of  claims 60 - 79 , wherein V H1  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         81 . The binding protein of any one of  claims 60 - 80 , wherein V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively. 
     
     
         82 . The binding protein of any one of  claims 60 - 80 , wherein V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         83 . The binding protein of any one of  claims 60 - 82 , wherein V H2  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         84 . The binding protein of any one of  claims 60 - 83 , wherein V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 comprising a sequence as set forth in SEQ ID NOs: 248, 497, and 250, respectively; a sequence as set forth in SEQ ID NOs: 251, 252, and 253, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 256, respectively; a sequence as set forth in SEQ ID NOs: 254, 255, and 498, respectively; a sequence as set forth in SEQ ID NOs: 257, 258, and 259, respectively; a sequence as set forth in SEQ ID NOs: 263, 264, and 265, respectively; a sequence as set forth in SEQ ID NOs: 499, 261, and 262, respectively; a sequence as set forth in SEQ ID NOs: 479, 480, and 481, respectively; a sequence as set forth in SEQ ID NOs: 482, 483, and 484, respectively; or a sequence as set forth in SEQ ID NOs: 485, 486, and 487, respectively. 
     
     
         85 . The binding protein of any one of  claims 60 - 83 , wherein V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         86 . The binding protein of any one of  claims 60 - 85 , wherein V H3  comprises a heavy chain variable domain comprising a sequence selected from the group consisting of SEQ ID NOs: 502, 503, 504, 505, 506, 507, 508, 509, 510, and 511. 
     
     
         87 . The binding protein of any one of  claims 60 - 86 , wherein V L1  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V L2  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V L3  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V H1  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; V H2  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; and V H3  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253. 
     
     
         88 . The binding protein of any one of  claims 60 - 86 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; and V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503. 
     
     
         89 . The binding protein of any one of  claims 60 - 88 , wherein V L1  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V L2  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V L3  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V H1  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; V H2  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; and V H3  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503. 
     
     
         90 . The binding protein of any one of  claims 60 - 86 , wherein V L1  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 494, a CDR-L2 comprising the sequence of SEQ ID NO: 495, and a CDR-L3 comprising the sequence of SEQ ID NO: 496; V L2  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 488, a CDR-L2 comprising the sequence of SEQ ID NO: 489, and a CDR-L3 comprising the sequence of SEQ ID NO: 490; V L3  comprises a CDR-L1 comprising the sequence of SEQ ID NO: 269, a CDR-L2 comprising the sequence of SEQ ID NO: 270, and a CDR-L3 comprising the sequence of SEQ ID NO: 271; V H1  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 485, a CDR-H2 comprising the sequence of SEQ ID NO: 486, and a CDR-H3 comprising the sequence of SEQ ID NO: 487; V H2  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 479, a CDR-H2 comprising the sequence of SEQ ID NO: 480, and a CDR-H3 comprising the sequence of SEQ ID NO: 481; and V H3  comprises a CDR-H1 comprising the sequence of SEQ ID NO: 251, a CDR-H2 comprising the sequence of SEQ ID NO: 252, and a CDR-H3 comprising the sequence of SEQ ID NO: 253. 
     
     
         91 . The binding protein of any one of  claims 60 - 86 , wherein V L1  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 524; V L2  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 522; V L3  comprises a CDR-L1, CDR-L2, and CDR-L3 of a light chain variable domain comprising the light chain variable domain sequence of SEQ ID NO: 513; V H1  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 511; V H2  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 509; and V H3  comprises a CDR-H1, CDR-H2, and CDR-H3 of a heavy chain variable domain comprising the heavy chain variable domain sequence of SEQ ID NO: 503. 
     
     
         92 . The binding protein of any one of  claims 60 - 86  and  90 - 91 , wherein V L1  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 524; V L2  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 522; V L3  comprises a light chain variable domain comprising the sequence of SEQ ID NO: 513; V H1  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 511; V H2  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 509; and V H3  comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 503. 
     
     
         93 . The binding protein of  claim 60 , wherein the second polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         94 . The binding protein of  claim 60 , wherein the third polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         95 . The binding protein of  claim 60 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         96 . The binding protein of  claim 60 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         97 . The binding protein of  claim 60 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         98 . The binding protein of  claim 61 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         99 . The binding protein of  claim 61 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         100 . The binding protein of  claim 61 , wherein the C H3  domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         101 . The binding protein of  claim 60  or  claim 61 , wherein at least one of L 1 , L 2 , L 3 , or L 4  is independently 0 amino acids in length. 
     
     
         102 . The binding protein of  claim 60  or  claim 61 , wherein L 1 , L 2 , L3, or L 4  are each independently at least one amino acid in length. 
     
     
         103 . The binding protein of any one of  claims 60 - 102 , wherein L 1  is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299). 
     
     
         104 . A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I]
   and a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1   [II]
 
   and a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1   [III]
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV]
 
   wherein:   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is the immunoglobulin C H1  heavy chain constant domain; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;   wherein:
 (a) V L1 , V L2  and V L3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or 
 (b) V L1 , V L2  and V L3  each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and 
   wherein:
 (a) V H1 , V H2 , and V H3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or 
 (b) V H1 , V H2 , and V H3  each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487. 
   
     
     
         105 . A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula:
   V L2 -L 1 -V L1 -L 2 -C L   [I]
   and a second polypeptide chain comprises a structure represented by the formula:
   V H1 -L 3 -V H2 -L 4 -C H1 -hinge-C H2 -C H3   [II]
 
   and a third polypeptide chain comprises a structure represented by the formula:
   V H3 -C H1 -hinge-C H2 -C H3   [III]
 
   and a fourth polypeptide chain comprises a structure represented by the formula:
   V L3 -C L   [IV]
 
   wherein:   V L1  is a first immunoglobulin light chain variable domain;   V L2  is a second immunoglobulin light chain variable domain;   V L3  is a third immunoglobulin light chain variable domain;   V H1  is a first immunoglobulin heavy chain variable domain;   V H2  is a second immunoglobulin heavy chain variable domain;   V H3  is a third immunoglobulin heavy chain variable domain;   C L  is an immunoglobulin light chain constant domain;   C H1  is the immunoglobulin C H1  heavy chain constant domain;   C H2  is an immunoglobulin C H2  heavy chain constant domain;   C H3  is an immunoglobulin C H3  heavy chain constant domain;   hinge is an immunoglobulin hinge region connecting the C H1  and C H2  domains; and   L 1 , L 2 , L 3 , and L 4  are amino acid linkers;   wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair;   wherein:
 (a) V L1 , V L2  and V L3  are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 303, 305, 311, 313, 319, 321, 327, 329, 335, 337, 343, 345, 351, 353, 359, 361, 367, 369, 375, 377, 383, 385, 391, 393, 399, 401, 407, 409, 415, 417, 423, 425, 431, 433, 439, 441, 447, 449, 455, 457, 463, 465, 471, 473; or 
 (b) V L1 , V L2  and V L3  each independently comprise light chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 266-271, 275-277, 488-496; and 
   wherein:
 (a) V H1 , V H2 , and V H 3 are each independently a variable domain derived from an amino acid sequence as set forth in any one of SEQ ID NOs: 302, 304, 310, 312, 318, 320, 326, 328, 334, 336, 342, 344, 350, 352, 358, 360, 366, 368, 374, 376, 382, 384, 390, 392, 398, 400, 406, 408, 414, 416, 422, 424, 430, 432, 438, 440, 446, 448, 454, 456, 462, 464, 470, 472; or 
 (b) V H1 , V H2 , and V H3  each independently comprise heavy chain complementarity determining regions of a variable domain comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 248-253, 257-259, 479-487. 
   
     
     
         106 . The binding protein of  claim 104 , wherein the second polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         107 . The binding protein of  claim 104 , wherein the third polypeptide chain further comprises an Fc region linked to C H1 , the Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains. 
     
     
         108 . The binding protein of  claim 104 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         109 . The binding protein of  claim 104 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the first Fc region comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, wherein the second Fc region comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         110 . The binding protein of  claim 104 , wherein the second polypeptide chain further comprises a first Fc region linked to C H1 , the first Fc region comprising an immunoglobulin hinge region and C H2  and C H3  immunoglobulin heavy chain constant domains, and wherein the third polypeptide chain further comprises a second Fc region linked to C H1 , the second Fc region comprising an immunoglobulin hinge region and C H2  and C H1  immunoglobulin heavy chain constant domains; wherein the first and second Fc regions comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         111 . The binding protein of  claim 105 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V. 
     
     
         112 . The binding protein of  claim 105 , wherein the C H3  domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C H3  domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W. 
     
     
         113 . The binding protein of  claim 105 , wherein the C H3  domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S. 
     
     
         114 . The binding protein of  claim 104  or  claim 105 , wherein at least one of L 1 , L 2 , L 3 , or L 4  is independently 0 amino acids in length. 
     
     
         115 . The binding protein of  claim 104  or  claim 105 , wherein L 1 , L 2 , L 3 , or L 4  are each independently at least one amino acid in length. 
     
     
         116 . The binding protein of any one of  claims 104 - 115 , wherein L 1  is Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ ID NO: 299). 
     
     
         117 . A binding protein comprising a first polypeptide chain, a second polypeptide chain, a third polypeptide chain and a fourth polypeptide chain wherein:
 (a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 305 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 305; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 304 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 302 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 302; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 303 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303;   (b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 313 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 313; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 312 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 312; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 310 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 310; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 311 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 311;   (c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 321 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 321; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 320 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 320; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 318 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 318; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 319 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 319;   (d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 329 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 329; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 328 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 328; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 326 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 326; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 327 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 327;   (e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 337 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 336 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 336; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 334 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 334; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 335 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 335;   (f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 345 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 345; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 344 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 344; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 342 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 342; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 343 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 343;   (g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 353 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 353; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:352; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 350 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 350; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 351 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 351;   (h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 361 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 361; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 360 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 360; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 358 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 358; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 359 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 359;   (i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 369 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 369; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 368 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 368; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 366 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 366; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 367 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 367;   (j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 377 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 377; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 376 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 376; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 374 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 374; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 375 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 375;   (k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 385 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 385; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 384 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 384; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 382 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 382; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 383 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 383;   (l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 393 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 393; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 392 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 392; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 390 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 390; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 391 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 391;   (m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 401 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 401; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 400 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 400; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 398 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 398; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 399 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 399;   (n) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 409 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 409; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 408 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 408; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 406 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 407 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 407;   (p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 417 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 417; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 416 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 416; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 414 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 414; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 415 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 415;   (q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 425 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 425; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 424 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 424; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 422 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 422; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 423 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 423;   (r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 433 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:433; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 432 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 432; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 430 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 430; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 431 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 431;   (s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 441 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 441; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 440 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 438 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 438; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 439 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439;   (t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 449 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 449; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 448 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 448; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 446 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 446; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 447 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 447,   (u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 457 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 457; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 456 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 456; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 454 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 454; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 455 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 455;   (v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 465 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 465; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 464 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 464; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 462 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 462; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 463 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 463; or   (w) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 473 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 473; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 472 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 472; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 470 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 470; and the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 471 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 471.   
     
     
         118 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding protein of any one of  claims 1 - 117 . 
     
     
         119 . An expression vector comprising the nucleic acid molecule of  claim 118 . 
     
     
         120 . An isolated host cell comprising the nucleic acid molecule of  claim 118 . 
     
     
         121 . An isolated host cell comprising the expression vector of  claim 119 . 
     
     
         122 . The isolated host cell of  claim 120  or  claim 121 , wherein the host cell is a mammalian cell or an insect cell. 
     
     
         123 . A vector system comprising one or more vectors encoding a first, second, third, and fourth polypeptide chain of a binding protein of any one of  claims 1 - 117 . 
     
     
         124 . The vector system of  claim 123 , wherein the vector system comprises a first vector encoding the first polypeptide chain of the binding protein, a second vector encoding the second polypeptide chain of the binding protein, a third vector encoding the third polypeptide chain of the binding protein, and a fourth vector encoding the fourth polypeptide chain of the binding protein. 
     
     
         125 . The vector system of  claim 123 , wherein the vector system comprises a first vector encoding the first and second polypeptide chains of the binding protein, and a second vector encoding the third and fourth polypeptide chains of the binding protein. 
     
     
         126 . The vector system of any one of  claims 123 - 125 , wherein the one or more vectors are expression vectors. 
     
     
         127 . An isolated host cell comprising the vector system of any one of  claims 123 - 126 . 
     
     
         128 . The isolated host cell of  claim 127 , wherein the host cell is a mammalian cell or an insect cell. 
     
     
         129 . A method of producing a binding protein, the method comprising:
 a) culturing a host cell of any one of  claims 120 - 122  and  claims 127 - 128  under conditions such that the host cell expresses the binding protein; and   b) isolating the binding protein from the host cell.   
     
     
         130 . A method of preventing and/or treating HIV infection in a patient comprising administering to the patient a therapeutically effective amount of at least one binding protein of any one of  claims 1 - 117 . 
     
     
         131 . The method of  claim 130 , wherein the binding protein is co-administered with standard anti-retroviral therapy. 
     
     
         132 . The method of  claim 130  or  claim 131 , wherein administration of the at least one binding protein results in the neutralization of one or more HIV virions. 
     
     
         133 . The method of any one of  claims 130 - 132 , wherein administration of the at least one binding protein results in the elimination of one or more latently and/or chronically HIV-infected cells in the patient. 
     
     
         134 . The method of any one of  claims 130 - 133 , wherein the patient is a human. 
     
     
         135 . The binding protein of any one of  claims 1 - 117  for the prevention or treatment of an HIV infection in a patient. 
     
     
         136 . The binding protein of  claim 135 , wherein the binding protein is co-administered with standard anti-retroviral therapy. 
     
     
         137 . The binding protein of  claim 135  or  claim 136 , wherein the binding protein causes the neutralization of one or more HIV virions in the patient. 
     
     
         138 . The binding protein of any one of  claims 135 - 137 , wherein the binding protein causes the elimination of one or more latently and/or chronically HIV-infected cells in the patient. 
     
     
         139 . The binding protein of any one of  claims 135 - 138 , wherein the patient is a human.