MHC conjugates useful in ameliorating autoimmunity

Abstract

The present invention is directed to complexes consisting essentially of an isolated MHC component and an autoantigenic peptide associated with the antigen binding site of the MHC component. These complexes are useful in treating autoimmune disease.

What is claimed is:  
     
         1 . A substantially pure MHC-peptide complex consisting essentially of an autoantigenic peptide and an isolated MHC component having an antigen binding site, wherein the autoantigenic peptide is associated with the antigen binding site.  
     
     
         2 . A complex of  claim 1  wherein the peptide is noncovalently associated with the antigen binding site.  
     
     
         3 . A complex of  claim 1  wherein the MHC component is soluble.  
     
     
         4 . A complex of  claim 1  wherein the peptide is between about 8 to about 15 amino acids.  
     
     
         5 . A complex of  claim 1  wherein an epitope on the peptide is recognized by an autoreactive T cell associated with multiple sclerosis.  
     
     
         6 . A complex of  claim 1  wherein the MHC component is Class II MHC.  
     
     
         7 . A complex of  claim 1  wherein the MHC component is isolated from spleen cells.  
     
     
         8 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the MHC-peptide complex of  claim 1 .  
     
     
         9 . A pharmaceutical composition of  claim 8  wherein the complex is inside a liposome.  
     
     
         10 . A pharmaceutical composition of  claim 8  wherein the complex is substantially free of carbohydrate moities.  
     
     
         11 . A pharmaceutical composition of  claim 8  wherein the concentration of the complex is between about 0.02% and about 1% by weight.  
     
     
         12 . A pharmaceutical composition of  claim 8  wherein the pharmaceutically acceptable carrier is phosphate buffered saline.  
     
     
         13 . A method of inducing anergy in autoreactive T cells in a mammal, the method comprising administering to the mammal a therapeutically effective dose of a complex consisting essentially of an autoantigenic peptide and an isolated MHC component having an antigen binding site, wherein the autoantigenic peptide is associated with the antigen binding site.  
     
     
         14 . A method of  claim 13  wherein the MHC component is Class II MHC.  
     
     
         15 . A method of  claim 13  wherein the complex is embedded in a lipid membrane.  
     
     
         16 . A method of  claim 13  wherein the T cells are associated with rheumatoid arthritis or multiple sclerosis.  
     
     
         17 . A method of treating autoimmune disease in a mammal, the method comprising administering to the mammal a therapeutically effective dose of the pharmaceutical composition comprising a pharmaceutically acceptable carrier and a purified MHC-peptide complex consisting essentially of an autoantigenic peptide and an isolated MHC component having an antigen binding site, wherein the autoantigenic peptide is associated with the antigen binding site.  
     
     
         18 . A method of  claim 17  wherein the mammal is a mouse.  
     
     
         19 . A method of  claim 18  wherein the effective dose is between about 50 μg and about 300 μg of the complex.  
     
     
         20 . A method of  claim 17  wherein the pharmaceutical composition is administered intravenously.  
     
     
         21 . A method of  claim 20  wherein the effective dose is between about 3 mg MHC-peptide complex per kg body weight and about 15 mg MHC-peptide complex per kg body weight.  
     
     
         22 . A method of  claim 17  wherein the autoimmune disease is rheumatoid arthritis or multiple sclerosis.  
     
     
         23 . A method for preparing a complex consisting essentially of an autoantigenic peptide and an isolated MHC component having an antigen binding site, the method comprising: 
 isolating the MHC component from a cell producing the component;    contacting the MHC component with the peptide such that the peptide is coupled to the antigen binding site; and    removing excess peptide not coupled to the antigen binding site.    
     
     
         24 . A method of  claim 23  wherein the step of removing excess peptide is carried out by dialysis.  
     
     
         25 . A method of  claim 23  further comprising the step of dialyzing the complex in the presence of lipids to form liposomes.  
     
     
         26 . A method of  claim 23  wherein the peptide is nocovalently bound to the antigen binding site.  
     
     
         27 . A method of  claim 23  wherein the MHC component is a Class II glycoprotein of the major histocompatibility complex.  
     
     
         28 . A method of  claim 23  wherein the peptide comprises amino acids 1-14 of MBP.