Clement, Mathew, Knezevic, Lea, Dockree, Tamsin, McLaren, James E., Ladell, Kristin, Miners, Kelly L., Llewellyn-Lacey, Sian, Rubina, Anzelika, Francis, Ore, Cole, David K., Sewell, Andrew K., Bridgeman, John S., Price, David A., van den Berg, Hugo A. and Wooldridge, Linda
2021.
CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor.
Proceedings of the National Academy of Sciences
118
(29)
, e2019639118.
10.1073/pnas.2019639118
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Abstract
CD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used two intrinsically controlled systems to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Additional Information: | This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
Funders: | Wellcome Trust |
Date of First Compliant Deposit: | 21 July 2021 |
Date of Acceptance: | 8 June 2021 |
Last Modified: | 31 Jan 2022 07:27 |
URI: | https://orca.cardiff.ac.uk/id/eprint/142669 |
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