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Why must T cells be cross-reactive?

Sewell, Andrew K. 2012. Why must T cells be cross-reactive? Nature Reviews Immunology 12 (9) , pp. 669-677. 10.1038/nri3279

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Abstract

Clonal selection theory proposed that individual T cells are specific for a single peptide–MHC antigen. However, the repertoire of αβ T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes, and a comprehensive system requires each T cell to recognize numerous peptides and thus be cross-reactive. This compromise on specificity has profound implications because the chance of any natural peptide–MHC ligand being an optimal fit for its cognate TCR is small, as there will almost always be more-potent agonists. Furthermore, any TCR raised against a specific peptide–MHC complex in vivo can only be the best available solution from the naive T cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This 'systems view' of TCR recognition provides a plausible cause for autoimmune disease and substantial scope for multiple therapeutic interventions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: Nature Publishing Group
ISSN: 1474-1733
Last Modified: 04 Jun 2017 04:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/41575

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