How some T cells escape tolerance induction.
A feature common to many animal models of autoimmune disease, for example, experimental allergic encephalomyelitis, experimental autoimmune myasthenia gravis and collagen-induced arthritis, is the presence of self-reactive T cells in healthy animals, which are activated to produce disease by immunization with exogenous antigen. It is unclear why these T cells are not deleted during ontogeny in the thymus and, having escaped tolerance induction, why they are not spontaneously activated by self-antigen. To investigate these questions, we have examined an experimental model in which mice are tolerant to an antigen despite the presence of antigen-reactive T cells. We find that the T cells that escape tolerance induction are specific for minor determinants on the antigen. We propose that these T cells evade tolerance induction because some minor determinants are only available in relatively low amounts after in vivo processing of the whole antigen. For the same reason, these T cells are not normally activated but can be stimulated under special circumstances to circumvent tolerance.
Gammon
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G
Department of Microbiology, University of California, Los Angeles 90024.
Sercarz
E
E
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D007108:Immune Tolerance; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D009113:Muramidase / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D009842:Oligopeptides; D009113:Muramidase