The self-directed T cell repertoire: its creation and activation.
The considerable breadth of the self-directed T cell repertoire has only fully been appreciated during this past decade. It is a potential repertoire which can be tapped in various ways, most evidently in the study of autoimmune diseases, when because of a variety of factors, there is enhanced processing and presentation of determinants on self antigens. In this review, we have focused on the engagement of this self-reactive repertoire and some of the rules involved, which are not always so obvious. The total "residual" self-reactive repertoire directed against a single antigen (that remains after negative selection) will be a heterogeneous assemblage of T cells - (a) high affinity T cells directed against determinants whose presentation during tolerance induction was prevented, eg. through competitive binding by neighboring determinants; (b) lower affinity T cells directed against well-presented (dominant), as well as poorly-presented (cryptic) determinants; and (c) high affinity T cells directed against poorly-presented determinants, which are only presented during inflammation. Under conditions that favor upregulation of previously cryptic self determinants, one or more of the above subsets of the 'protected' T cell repertoires can be stimulated by these self determinants, leading to induction of autoreactivity. The latter could eventually result in autoimmunity under permissive conditions governed by MHC and non-MHC genes. Interestingly, the very same repertoires that appear to be recruited into pathogenic autoimmune destruction may be alternatively manipulated as a source of anti-cancer treatment. It is now evident that many tumor antigens are unmutated self antigens, and cryptic determinants within such tumor antigens could be used to recruit the anticryptic T cell repertoire for induction of anti-tumor immunity.
Moudgil
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Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201, USA. Kmoud001@umaryland.edu
Sercarz
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D000818:Animals; D000941:Antigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018716:Molecular Mimicry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000941:Antigens