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Why must T cells be cross-reactive?
Open accessAbstract
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.
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Citations
Cites
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How many TCR clonotypes does a body maintain?
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“Estimates of the number of different TCRs that could, in principle, be produced by VDJ gene rearrangement in the thymus, under the CC BY license (http://creativecommons.org/licenses/by/4.0/). are about 1015 (Sewell, 2012; Nikolich-Žugich et al., 2004; Zarnitsyna et al., 2013; Murugan et al., 2012).”
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Circadian and circannual timescales interact to generate seasonal changes in immune function
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Metadata
- Authors
- Sewell, A. K.
- Venue
- Nature Reviews Immunology
- Published
- 2012-08-24
- Volume
- 12
- Issue
- 9
- Pages
- 669-677
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2049204549
- Cited by
- 541
- References
- 2
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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