Analysis of TCR V beta gene usage and encephalitogenicity of myelin basic protein peptide p91-103 reactive T cell clones in SJL mice: lack of evidence for V gene hypothesis.
We have analyzed the epitope specificity and encephalitogenicity of peptides that span the C terminus of MBP, p84-103. Our studies show that multiple antigenic epitopes with disease-inducing capacity exist in SJL mice. Three peptides that span this region were examined and found to be immunogenic. However, the mode of immunization (active or passive) determined the incidence and severity of EAE. In our experiments adoptive transfer of p91-103-reactive T cell lines was most consistent in the development of disease. Interestingly, the response to peptides p89-101, p91-103, and p84-102 was absent following immunization with MBP. This suggests that although p91-103 and p89-101 were encephalitogenic they were not the major immunogenic epitopes following immunization with MBP. Analysis of a panel of eight p91-103-reactive T cell clones showed significant heterogeneity in the fine specificity, the TCR V beta gene usage, and in their ability of transfer EAE. These studies suggest that in SJL mice the epitopes involved in the pathogenesis of disease are multiple and there is no clear correlation between encephalitogenicity and TCR V beta gene usage. These observations argue against the presence of a dominant TCR V beta gene in the pathogenesis of EAE in SJL mice.
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Department of Neurology, University of Vermont, Burlington 05405.
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D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta