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How some T cells escape tolerance induction

Abstract

A FEATURE common to many animal models of autoimmune disease, for example, experimental allergic encephalomyelitis1, experimental autoimmune myasthenia gravis2 and collagen-induced arthritis3, 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 cells4. 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.

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Gammon, G., Sercarz, E. How some T cells escape tolerance induction. Nature 342, 183–185 (1989). https://doi.org/10.1038/342183a0

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