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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
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 | ||||||||||
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| 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: |
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| 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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