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

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Dockree, Tamsin, Holland, Christopher J., Clement, Mathew, Ladell, Kristin, McLaren, James E., Berg, Hugo van den, Gostick, Emma, L. Miners, Kelly, Llewellyn-Lacey, Sian, S Bridgeman, John, Man, Stephen, Bailey, Mick, Burrows, Scott R., Price, David A. and Wooldridge, Linda (2017) CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology, 95 . pp. 68-76. doi:10.1038/icb.2016.85

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Official URL: http://dx.doi.org/10.1038/icb.2016.85

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Abstract

The CD8 co-receptor 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.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Science, Engineering and Medicine > Science > Mathematics
Library of Congress Subject Headings (LCSH): Cellular immunity, Antigens
Journal or Publication Title: Immunology and Cell Biology
Publisher: Nature Publishing Group
ISSN: 0818-9641
Official Date: January 2017
Dates:
DateEvent
January 2017Published
8 November 2016Available
28 July 2016Accepted
9 November 2015Submitted
Volume: 95
Page Range: pp. 68-76
DOI: 10.1038/icb.2016.85
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Wellcome Trust (London, England)
Grant number: WT099067AIA, 100326/Z/12/Z, WT079848MA, WT096454AIA
Adapted As: .

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