CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor

Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Knezevic, Lea, Dockree, Tamsin, McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Miners, Kelly L., Llewellyn-Lacey, Sian, Rubina, Anzelika, Francis, Ore, Cole, David K. ORCID: https://orcid.org/0000-0003-0028-9396, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Bridgeman, John S., Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, 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
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:	18 Sep 2023 18:18
URI:	https://orca.cardiff.ac.uk/id/eprint/142669

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