Analysis of TCR beta chains in Lewis rats with experimental allergic encephalomyelitis. II. Vbeta8.2+ T cells with limited CDR3 N region additions derive from the adult thymus.
Immunization of Lewis (LEW) rats with guinea pig myelin basic protein (MBP) induces a population of encephalitogenic CD4 T cells having specificity for the dominant immunogenic peptide of MBP, 68-86. The TCR beta chains of these disease-causing T cells show three distinct features: they are almost exclusively Vbeta8.2, they use AspSer as the first two amino acid residues of the third complementarity-determining region (CDR3) and these junctional region sequences show few if any non-germline N-region nucleotide additions. This last feature raises the possibility that these autoimmune T cell precursors derive from TCR gene rearrangements occurring during early, perinatal ontogeny, a period when the enzyme terminal deoxynucleotidyl transferase (TdT), responsible for N region additions, is not expressed. An alternative possibility is that these features of the TCR of MBP 68-86-reactive T cells are dictated by considerations of antigen selection throughout ontogeny both in the thymus and in the periphery--ie., that such beta chains are conformationally the most appropriate for triggering by an epitope of 68-86 complexed to class II RT1.BI MHC molecules. We show here that active experimental allergic encephalomyelitis, while delayed in onset, occurs in heavily irradiated animals, but not in the absence of a thymus, a finding indicating that this autoimmune disease is caused by a T cell subpopulation derived from the post-irradiation adult thymus. These disease-causing T cells are heavily Vbeta8.2+, CDR3 AspSer+ and use few N region additions. We conclude that T cells with these TCR beta chain features can be generated in the adult thymus and most likely reflect requirements imposed by antigen selection.
Wilson
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Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA. darcywilso@aol.com
Schroder
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Mueller
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Golding
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Wilson
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Gold
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D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
D016693:Receptors, Antigen, T-Cell, alpha-beta