Dockree, Tamsin, Holland, Christopher J., Clement, Mathew ![]() ![]() ![]() ![]() ![]() |
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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 |
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Date Type: | Publication |
Status: | Published |
Schools: | 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: | 16 Feb 2025 18:22 |
URI: | https://orca.cardiff.ac.uk/id/eprint/94125 |
Citation Data
Cited 14 times in Scopus. View in Scopus. Powered By Scopus® Data
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