CD4+ T Cells Recognize Conserved Influenza A Epitopes through Shared Patterns of V-Gene Usage and Complementary Biochemical Features

Alexander Greenshields-Watson, Meriem Attaf, Bruce J. MacLachlan, Thomas Whalley, Cristina Rius, Aaron Wall, Angharad Lloyd, Hywel Hughes, Kathryn E. Strange, Georgina H. Mason, Andrea J. Schauenburg, Sarah L. Hulin-Curtis, James Geary, Yuan Chen, Sarah N. Lauder, Kathryn Smart, Dhanasekaran Vijaykrishna, Miguel L. Grau, Mikhail Shugay, Robert AndrewsGarry Dolton, Pierre J. Rizkallah, Awen M. Gallimore, Andrew K. Sewell, Andrew J. Godkin, David K. Cole

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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.

Original languageEnglish
Article number107885
Number of pages15
JournalCell Reports
Issue number2
Publication statusPublished - 14 Jul 2020


  • biochemistry
  • CD4 T cells
  • clonotyping
  • HLA class II
  • immunology
  • influenza
  • peptide epitopes
  • pHLA mutlimer
  • T cell receptor
  • X-ray crystallography

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