Antigen-specific therapy of experimental allergic encephalomyelitis by soluble class II major histocompatibility complex-peptide complexes.
Experimental allergic encephalomyelitis is a T-cell-mediated, major histocompatibility complex (MHC) class II gene-linked autoimmune demyelinating disease of the central nervous system. To develop therapies that will specifically inactivate only the autoantigen-reactive T cells, mice were treated with soluble MHC class II molecules that had been complexed with encephalitogenic peptides. Intravenous injections of 300 micrograms of complexes consisting of encephalitogenic peptide 91-103 of myelin basic protein plus I-As protein on day 0, 4, and 7 were effective in preventing experimental allergic encephalomyelitis. Similarly, administration of 45 micrograms of I-As protein complexed to peptide 139-151 from proteolipoprotein on day 1, 4, and 7 prevented mortality and significantly reduced paralysis induced by immunization with the encephalitogenic proteolipoprotein peptide. Histological examination of sections of animal brains revealed that treatment with I-As protein plus myelin basic protein 91-103 peptide prevents the development of inflammatory lesions characteristic of experimental allergic encephalomyelitis. Thus, treatment with MHC-self-peptide complexes could serve as a highly specific therapeutic modality in treating autoimmune disease when the putative autoantigen and the MHC restricting elements are known.
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Anergen, Inc., Redwood City, CA 94063.
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D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000276:immunology / Q000473:pathology; D002846:Chromatography, Affinity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000302:isolation & purification; D007167:Immunotherapy; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D010455:Peptides