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CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features

Greenshields-Watson, Alexander, Attaf, Meriem, MacLachlan, Bruce J., Whalley, Thomas, Rius, Cristina, Wall, Aaron, Lloyd, Angharad, Hughes, Hywel, Strange, Kathryn E., Mason, Georgina H., Schauenburg, Andrea J., Hulin-Curtis, Sarah L., Geary, James, Chen, Yuan, Lauder, Sarah N., Smart, Kathryn, Vijaykrishna, Dhanasekaran, Grau, Miguel L., Shugay, Mikhail, Andrews, Robert, Dolton, Garry, Rizkallah, Pierre J., Gallimore, Awen M., Godkin, Andrew J., Sewell, Andrew J. and Cole, David K. 2020. CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features. Cell Reports 32 (2) , 107885. 10.1016/j.celrep.2020.107885

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T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+ T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+ T cells. Here, we investigate CD4+ T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+ T cells in five HLA-DR1+ subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article under the terms of the CC-BY license.
Publisher: Elsevier
ISSN: 2211-1247
Funders: Wellcome Trust
Date of First Compliant Deposit: 23 July 2020
Date of Acceptance: 17 June 2020
Last Modified: 17 Mar 2021 03:01

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