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

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

  • Cell Rep. 2020 Jul 14;32(2):107885. doi: 10.1016/j.celrep.2020.107885.
Alexander Greenshields-Watson 1,  Meriem Attaf 1,  Bruce J MacLachlan 2,  Thomas Whalley 1,  Cristina Rius 1,  Aaron Wall 1,  Angharad Lloyd 1,  Hywel Hughes 1,  Kathryn E Strange 1,  Georgina H Mason 1,  Andrea J Schauenburg 1,  Sarah L Hulin-Curtis 1,  James Geary 1,  Yuan Chen 1,  Sarah N Lauder 1,  Kathryn Smart 1,  Dhanasekaran Vijaykrishna 3,  Miguel L Grau 3,  Mikhail Shugay 4,  Robert Andrews 1,  Garry Dolton 1,  Pierre J Rizkallah 1,  Awen M Gallimore 1,  Andrew K Sewell 1,  Andrew J Godkin 5,  David K Cole 6
Affiliations

Affiliations

  • 1 Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
  • 2 Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia.
  • 3 Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia.
  • 4 Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia.
  • 5 Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Department of Gastroenterology, Hepatology and Endoscopy, University Hospital of Wales, Cardiff, UK. Electronic address: [email protected].
  • 6 Cardiff University, School of Medicine, Heath Park, Cardiff, UK. Electronic address: [email protected].
PMID: 32668259 DOI: 10.1016/j.celrep.2020.107885
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.

Keywords

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

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