Antigen-specific therapy of experimental allergic encephalomyelitis by soluble class II major histocompatibility complex-peptide complexes.

Abstract

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.

• Authors: S D Sharma, B Nag, X M Su, D Green, E Spack, B R Clark, S Sriram
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 88 Issue 24 Pg. 11465-9 (Dec 15 1991) ISSN: 0027-8424 [Print] United States
• PMID: 1722335 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Histocompatibility Antigens Class II
• Myelin Basic Protein
• Myelin Proteins
• Myelin Proteolipid Protein
• Peptide Fragments
• Peptides

Topics

• Animals
• Antibodies, Monoclonal
• Brain (immunology, pathology)
• Chromatography, Affinity
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology, therapy)
• Female
• Histocompatibility Antigens Class II (immunology, isolation & purification)
• Immunotherapy
• Mice
• Mice, Inbred Strains
• Myelin Basic Protein (immunology)
• Myelin Proteins (immunology)
• Myelin Proteolipid Protein
• Peptide Fragments (immunology)
• Peptides (chemical synthesis, immunology)
• Spleen (immunology)