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CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

Dockree, Tamsin, Holland, Christopher J., Clement, Mathew, Ladell, Kristin Ingrid, McLaren, James Edward, Van Den Berg, Hugo A., Gostick, Emma, Llewellyn-Lacey, Sian, Man, Stephen Tzekwung, Bailey, Mick, Burrows, Scott, Price, David and Wooldridge, Linda 2017. CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology 95 (1) , pp. 68-76. 10.1038/icb.2016.85

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Abstract

The CD8 coreceptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR) binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~ 1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~ 10-fold). In this study, we used a panel of MHCI mutants with altered CD8 binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity. The pMHCI/CD8 interaction controls specificity

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QL Zoology
Publisher: Nature Publishing Group
ISSN: 0818-9641
Funders: Wellcome Trust
Date of First Compliant Deposit: 8 September 2016
Date of Acceptance: 28 July 2016
Last Modified: 13 Aug 2019 08:57
URI: http://orca.cf.ac.uk/id/eprint/94125

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