Compositions and methods for modulating lymphocyte activity

Abstract

The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies B7 family member B7x as interacting with BTLA to attenuate lymphocyte activity. Methods and compositions for modulating BTLA-mediated negative signaling and interfering with the interaction of BTLA and B7x for therapeutic, diagnostic and research purposes are also provided.

1 - 19 . (canceled) 
     
     
         20 . An antibody that specifically binds a protein comprising an amino acid sequence having at least about 95% identity to the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         21 . The antibody of  claim 20 , wherein the antibody is capable of inhibiting the ability of BTLA protein to bind a natural ligand. 
     
     
         22 . The antibody of  claim 20 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         23 . The antibody of  claim 20 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         24 . The antibody of  claim 20 , wherein the antibody is capable of stimulating activation of SHP-1. 
     
     
         25 . The antibody of  claim 20 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         26 . The antibody of  claim 20 , wherein the antibody is capable of inducing phosphorylation of BTLA protein. 
     
     
         27 . The antibody of  claim 20 , wherein the antibody is capable of reducing BTLA protein-mediated negative signaling. 
     
     
         28 . The antibody of  claim 20 , wherein the antibody specifically binds to an epitope in an extracellular domain of BTLA protein. 
     
     
         29 . The antibody of  claim 28 , wherein the antibody is capable of inhibiting the ability of BTLA protein to bind to a natural ligand. 
     
     
         30 . The antibody of  claim 28 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         31 . The antibody of  claim 28 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         32 . The antibody of  claim 28 , wherein the antibody is capable of stimulating activation of SHP-1. 
     
     
         33 . The antibody of  claim 28 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         34 . The antibody of  claim 28 , wherein the antibody is capable of inducing phosphorylation of BTLA protein. 
     
     
         35 . The antibody of  claim 28 , wherein the antibody is capable of reducing BTLA protein-mediated negative signaling. 
     
     
         36 . The antibody of  claim 20 , wherein the antibody binds to an epitope between about residue 31 to about residue 153 of the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         37 . The antibody of  claim 36 , wherein the antibody is capable of inhibiting the ability of BTLA protein to bind to a natural ligand. 
     
     
         38 . The antibody of  claim 36 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         39 . The antibody of  claim 36 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         40 . The antibody of  claim 36 , wherein the antibody is capable of stimulating activation of SHP-1. 
     
     
         41 . The antibody of  claim 36 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         42 . The antibody of  claim 36 , wherein the antibody is capable of inducing phosphorylation of BTLA protein. 
     
     
         43 . The antibody of  claim 36 , wherein the antibody is capable of reducing BTLA protein-mediated negative signaling. 
     
     
         44 . An antibody that specifically binds a protein comprising an amino acid sequence having at least about 95% identity to the amino acid sequence set forth in SEQ ID NO:6. 
     
     
         45 . The antibody of  claim 44 , wherein the antibody is capable of inhibiting the binding of BTLA protein to a natural ligand. 
     
     
         46 . The antibody of  claim 44 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         47 . The antibody of  claim 44 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         48 . The antibody of  claim 44 , wherein the antibody is capable of stimulating activation of SHP-1. 
     
     
         49 . The antibody of  claim 44 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         50 . The antibody of  claim 44 , wherein the antibody is capable of inducing the phosphorylation of BTLA protein. 
     
     
         51 . The antibody of  claim 44 , wherein the antibody is capable of reducing BTLA protein-mediated negative signaling. 
     
     
         52 . The antibody of  claim 44 , wherein the antibody specifically binds to an epitope in an extracellular domain of BTLA protein. 
     
     
         53 . The antibody of  claim 52 , wherein the antibody is capable of inhibiting the ability of BTLA to bind a natural ligand. 
     
     
         54 . The antibody of  claim 52 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         55 . The antibody of  claim 52 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         56 . The antibody of  claim 52 , wherein the antibody is capable of stimulating activation of SHP-1. 
     
     
         57 . The antibody of  claim 52 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         58 . The antibody of  claim 52 , wherein the antibody is capable of inducing phosphorylation of BTLA protein. 
     
     
         59 . The antibody of  claim 52 , wherein the antibody is capable of reducing BTLA protein-mediated negative signaling. 
     
     
         60 . The antibody of  claim 44 , wherein the antibody specifically binds to an extracellular domain of BTLA protein, the extracellular domain comprising the Ig domain of the amino acid sequence set forth in SEQ ID NO:6. 
     
     
         61 . The antibody of  claim 60 , wherein the antibody is capable of inhibiting the ability of BTLA protein to bind a natural ligand. 
     
     
         62 . The antibody of  claim 60 , wherein the antibody is capable of reducing or eliminating one or more biological functions of BTLA protein. 
     
     
         63 . The antibody of  claim 60 , wherein the antibody is capable of stimulating BTLA protein-mediated negative signaling. 
     
     
         64 . The antibody of  claim 60 , wherein the antibody is capable of stimulating the activation of SHP-1. 
     
     
         65 . The antibody of  claim 60 , wherein the antibody is capable of stimulating activation of SHP-2. 
     
     
         66 . The antibody of  claim 60 , wherein the antibody is capable of inducing phosphorylation of BTLA protein. 
     
     
         67 . The antibody of  claim 60 , wherein the antibody is capable of reducing BTLA-mediated negative signaling. 
     
     
         68 . An anti-BTLA antibody capable of inhibiting the ability of BTLA protein to bind a natural ligand. 
     
     
         69 . An anti-BTLA antibody capable of reducing or eliminating one or more biological functions of BTLA protein.