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: https://orcid.org/0000-0002-1896-1649, Wall, Aaron, Lloyd, Angharad, Hughes, Hywel, Strange, Kathryn E., Mason, Georgina H., Schauenburg, Andrea J., Hulin-Curtis, Sarah L. ORCID: https://orcid.org/0000-0003-0889-964X, Geary, James, Chen, Yuan, Lauder, Sarah N., Smart, Kathryn, Vijaykrishna, Dhanasekaran, Grau, Miguel L., Shugay, Mikhail, Andrews, Robert, Dolton, Garry, Rizkallah, Pierre J. ORCID: https://orcid.org/0000-0002-9290-0369, Gallimore, Awen M. ORCID: https://orcid.org/0000-0001-6675-7004, Godkin, Andrew J. ORCID: https://orcid.org/0000-0002-1910-7567, Sewell, Andrew J. ORCID: https://orcid.org/0000-0003-3194-3135 and Cole, David K. ORCID: https://orcid.org/0000-0003-0028-9396 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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Abstract

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:	Advanced Research Computing @ Cardiff (ARCCA) 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:	25 Jul 2024 16:10
URI:	https://orca.cardiff.ac.uk/id/eprint/133664

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