Pathogenicity of T cells responsive to diverse cryptic epitopes of myelin basic protein in the Lewis rat.
The cellular immunology of experimental autoimmune encephalomyelitis, a model for multiple sclerosis, has been studied, for the most part, using T cells directed to dominant epitopes of the Ag myelin basic protein (MBP). To characterize T cells reactive to cryptic epitopes of MBP, we immunized Lewis rats with each of 17 overlapping peptides of the 18.5-kDa isoform of rat MBP. We found that, in addition to the known 71-90 epitope, six other peptides induced active encephalomyelitis in the majority the injected rats. T cell lines raised to six different MBP epitopes were encephalitogenic upon adoptive transfer to naive rats. In contrast to the T cells specific for the dominant 71-90 peptide, the T cell lines reactive to cryptic epitopes were not restricted in their TCR genes to V beta 8.2, and some of the lines caused prolonged disease. Thus, T cells of different specificities and TCR usage can be pathogenic.
Mor
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Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Cohen
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D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D004676:Myelin Basic Protein; D010455:Peptides