Regulatory t cell epitopes, compositions and uses thereof

Abstract

The invention is directed to T cell epitopes wherein said epitopes comprises a peptide or polypeptide chain comprising at least a portion of an immunoglobulin constant or variable region. The invention also relates to methods of using and methods of making the epitopes of the invention.

What is claimed is: 
     
         1 . A method for enhancing the immunogenicity of an Immunoglobulin-G (IgG)-containing molecule comprising an IgG antibody, comprising identification and removal of one or more regulatory T cell epitopes from the IgG antibody, wherein the one or more regulatory T cell epitopes are selected from the group consisting of: SEQ ID NOS: 4-37 and wherein said regulatory T cell epitopes are modified such that they no longer bind to MHC class molecules and regulatory T cells. 
     
     
         2 . The method of  claim 1 , comprising identification and removal of one or more regulatory T cell epitopes in a heavy chain constant region of the IgG antibody, wherein the one or more regulatory T cell epitopes are selected from the group consisting of: SEQ ID NOS: 4-5. 
     
     
         3 . The method of  claim 1 , comprising identification and removal of one or more regulatory T cell epitopes in a heavy chain variable region of the IgG antibody, wherein the one or more regulatory T cell epitopes are selected from the group consisting of: SEQ ID NOS: 6-22. 
     
     
         4 . The method of  claim 1 , comprising identification and removal of one or more regulatory T cell epitopes in a light chain constant region of the IgG antibody, wherein the one or more regulatory T cell epitopes are selected from the group consisting of: SEQ ID NOS: 23-24. 
     
     
         5 . The method of  claim 1 , comprising identification and removal of one or more regulatory T cell epitopes in a light chain variable region of the IgG antibody, wherein the one or more regulatory T cell epitopes are selected from the group consisting of SEQ ID NOS: 25-37. 
     
     
         6 . The method of  claim 1 , wherein the IgG antibody is selected from the group consisting of an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody. 
     
     
         7 . An isolated IgG-containing molecule comprising a modified IgG antibody, wherein the modified IgG antibody has been altered to remove one or more regulatory T cell epitopes, wherein said one or more regulatory T cell epitopes is selected from the group consisting of: SEQ ID NOS: 4-37. 
     
     
         8 . The isolated IgG-containing molecule of  claim 7 , wherein the modified IgG antibody comprises a modified IgG heavy chain constant region, wherein the IgG heavy chain constant region has been altered to remove one or more regulatory T cell epitopes, wherein said one or more regulatory T cell epitopes is selected from the group consisting of: SEQ ID NOS: 4-5. 
     
     
         9 . The isolated IgG-containing molecule of  claim 7 , wherein the modified IgG antibody comprises a modified IgG heavy chain variable region, wherein the IgG heavy chain variable region has been altered to remove one or more regulatory T cell epitopes, wherein said one or more regulatory T cell epitopes is selected from the group consisting of: SEQ ID NOS: 6-22. 
     
     
         10 . The isolated IgG-containing molecule of  claim 7 , wherein the modified IgG antibody comprises a modified IgG light chain constant region, wherein the IgG light chain constant region has been altered to remove one or more regulatory T cell epitopes, wherein said one or more regulatory T cell epitopes is selected from the group consisting of: SEQ ID NOS: 23-24. 
     
     
         11 . The isolated IgG-containing molecule of  claim 7 , wherein the modified IgG antibody comprises a modified IgG light chain variable region, wherein the IgG light chain variable region has been altered to remove one or more regulatory T cell epitopes, wherein said one or more regulatory T cell epitopes is selected from the group consisting of: SEQ ID NOS: 25-37. 
     
     
         12 . The isolated IgG-containing molecule of  claim 7 , wherein the IgG antibody is selected from the group consisting of an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody. 
     
     
         13 . A method for enhancing the immunogenicity of an Fc-containing molecule comprising an IgG antibody Fc domain, comprising identification and removal of one or more regulatory T cell epitopes, wherein the one or more regulatory T cell epitopes comprises SEQ ID NO: 4. 
     
     
         14 . The method of  claim 13 , wherein the IgG antibody Fc domain is selected from the group consisting of an an IgG1 antibody Fc domain, an IgG2 antibody Fc domain, an IgG3 antibody Fc domain, and an IgG4 antibody Fc domain. 
     
     
         15 . A modified Fc-containing molecule comprising a modified IgG antibody Fc domain, wherein the modified Fc domain has been altered to remove one or more regulatory T cell epitopes, wherein the one or more regulatory T cell epitopes comprises SEQ ID NO: 4. 
     
     
         16 . The modified Fc-containing molecule of  claim 15 , wherein the IgG antibody Fc domain is selected from the group consisting of an IgG1 antibody Fc domain, an IgG2 antibody Fc domain, an IgG3 antibody Fc domain, and an IgG4 antibody Fc domain.