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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 ORCID:, Wall, Aaron, Lloyd, Angharad, Hughes, Hywel, Strange, Kathryn E., Mason, Georgina H., Schauenburg, Andrea J., Hulin-Curtis, Sarah L. ORCID:, Geary, James, Chen, Yuan, Lauder, Sarah N., Smart, Kathryn, Vijaykrishna, Dhanasekaran, Grau, Miguel L., Shugay, Mikhail, Andrews, Robert, Dolton, Garry, Rizkallah, Pierre J. ORCID:, Gallimore, Awen M. ORCID:, Godkin, Andrew J. ORCID:, Sewell, Andrew J. ORCID: and Cole, David K. ORCID: 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: 15 May 2024 01:08

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