Cell Reports (Jul 2020)
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 Andrews,
- Garry Dolton,
- Pierre J. Rizkallah,
- Awen M. Gallimore,
- Andrew K. Sewell,
- Andrew J. Godkin,
- David K. Cole
Affiliations
- Alexander Greenshields-Watson
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Meriem Attaf
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Bruce J. MacLachlan
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia
- Thomas Whalley
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Cristina Rius
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Aaron Wall
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Angharad Lloyd
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Hywel Hughes
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Kathryn E. Strange
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Georgina H. Mason
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Andrea J. Schauenburg
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Sarah L. Hulin-Curtis
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- James Geary
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Yuan Chen
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Sarah N. Lauder
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Kathryn Smart
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Dhanasekaran Vijaykrishna
- Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia
- Miguel L. Grau
- Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia
- Mikhail Shugay
- Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia
- Robert Andrews
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Garry Dolton
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Pierre J. Rizkallah
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Awen M. Gallimore
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Andrew K. Sewell
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK
- Andrew J. Godkin
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Department of Gastroenterology, Hepatology and Endoscopy, University Hospital of Wales, Cardiff, UK; Corresponding author
- David K. Cole
- Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Corresponding author
- Journal volume & issue
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Vol. 32,
no. 2
p. 107885
Abstract
Summary: 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.
