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

Clement, Mathew ORCID:, Knezevic, Lea, Dockree, Tamsin, McLaren, James E. ORCID:, Ladell, Kristin ORCID:, Miners, Kelly L., Llewellyn-Lacey, Sian, Rubina, Anzelika, Francis, Ore, Cole, David K. ORCID:, Sewell, Andrew K. ORCID:, Bridgeman, John S., Price, David A. ORCID:, 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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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

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