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CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor
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Clement, Mathew, Knezevic, L., Dockree, Tamsin, McLaren, J. E., Ladell, Kristin, Miners, K. L., Llewelly-Lacey, S., Rubina, A., Francis, O., Cole, D. K., Sewell, A. K., Bridgeman, J. S., Price, David A., van den Berg, H. 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 of the United States of America, 118 (29). e2019639118. doi:10.1073/pnas.2019639118 ISSN 0027-8424.
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Official URL: https://doi.org/10.1073/pnas.2019639118
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: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QR Microbiology | |||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | |||||||||||||||
Library of Congress Subject Headings (LCSH): | T-cell receptor genes , Major histocompatibility complex, T cells -- Differentiation, T cells -- Receptors -- Mathematical models | |||||||||||||||
Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | |||||||||||||||
Publisher: | National Academy of Sciences | |||||||||||||||
ISSN: | 0027-8424 | |||||||||||||||
Official Date: | 2021 | |||||||||||||||
Dates: |
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Volume: | 118 | |||||||||||||||
Number: | 29 | |||||||||||||||
Article Number: | e2019639118 | |||||||||||||||
DOI: | 10.1073/pnas.2019639118 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 23 June 2021 | |||||||||||||||
Date of first compliant Open Access: | 21 July 2021 | |||||||||||||||
RIOXX Funder/Project Grant: |
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