Methods of using multivalent mhc class ii-peptide chimeras

Abstract

The present invention provides a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker. Methods of making and using the multimeric complexes are also provided.

1 - 14 . (canceled) 
     
     
         15 . A method of modulating down-regulating or inhibiting T cell function comprising administering to a subject a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker, wherein each MHC element comprises all or part of an extracellular domain of an MHC molecule. 
     
     
         16 . The method of  claim 15  wherein the subject is affected by Type I diabetes and the peptide is a diabetes autoantigen. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 15  wherein the multimeric complex comprises two chimeric molecules. 
     
     
         19 . The method of  claim 15  wherein the multimeric complex comprises four chimeric molecules. 
     
     
         20 . The method of  claim 15  wherein the immunoglobulin constant region element of the multimeric complex comprises the CH3, CH2 and hinge regions of two heavy chains and the chains are linked by at least one disulfide bond. 
     
     
         21 . The method of  claim 15  wherein each MHC element of the multimeric complex comprises the extracellular domains of the α and β chains of an MHC class II molecule. 
     
     
         22 . The method of  claim 15  wherein the peptide of the multimeric complex is part of an autoantigen. 
     
     
         23 . The method of  claim 15  wherein the peptide of the multimeric complex is a diabetes autoantigen. 
     
     
         24 . The method of  claim 15  wherein the wherein the polyalkylene glycol of the multimeric complex is polyethylene glycol. 
     
     
         25 . The method of  claim 15  wherein the multimeric complex further comprises a toxin. 
     
     
         26 . The method of  claim 15  wherein the polyalkylene glycol linker of the multimeric complex is difunctional-polyalkylene glycol linker. 
     
     
         27 . The method of  claim 15  wherein the polyethylene glycol linker of the multimeric complex is diamino-polyethylene glycol linker. 
     
     
         28 . The method of  claim 15  wherein the difunctional-polyalkylene glycol linker of the multimeric complex is diamino-polyethylene glycol linker having a molecular weight of between about 1000-5000. 
     
     
         29 . The method of  claim 15  wherein the difunctional-polyalkylene glycol linker of the multimeric complex is diamino-polyethylene glycol linker having a molecular weight of 3400. 
     
     
         30 . A method of down-regulating or inhibiting T cell function comprising administering to a subject a multimeric complex of at least two chimeric molecules wherein each chimeric molecule comprises: an immunoglobulin constant region element having two chains covalently joined by a disulfide linkage wherein the chains comprise the CH3, CH2 and hinge domains; two MHC class II elements comprising the extracellular domains of the α and β chains, wherein each of the MHC elements is covalently linked via the α or β chain to a chain of the immunoglobulin constant region element; and an associated peptide covalently linked or fused to the MHC element; and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyethylene glycol linker.