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CD4+ T cells recognize conserved influenza a epitopes through shared patterns of V-gene usage and complementary biochemical features

DOI: 10.1016/j.celrep.2020.107885 DOI Help

Authors: Alexander Greenshields-watson (Cardiff University) , Meriem Attaf (Cardiff University) , Bruce J. Maclachlan (Cardiff University; Monash Biomedicine Discovery Institute) , Thomas Whalley (Cardiff University) , Cristina Rius (Cardiff University) , Aaron Wall (Cardiff University) , Angharad Lloyd (Cardiff University) , Hywel Hughes (Cardiff University) , Kathryn E. Strange (Cardiff University) , Georgina H. Mason (Cardiff University) , Andrea J. Schauenburg (Cardiff University) , Sarah L. Hulin-curtis (Cardiff University) , James Geary (Cardiff University) , Yuan Chen (Cardiff University) , Sarah N. Lauder (Cardiff University) , Kathryn Smart (Cardiff University) , Dhanasekaran Vijaykrishna , Miguel L. Grau (Monash Biomedicine Discovery Institute) , Mikhail Shugay (Skolkovo Institute of Science and Technology) , Robert Andrews (Cardiff University) , Garry Dolton (Cardiff University) , Pierre J. Rizkallah (Cardiff University) , Awen M. Gallimore (Cardiff University) , Andrew K. Sewell (Cardiff University) , Andrew J. Godkin (Cardiff University; University Hospital of Wales) , David K. Cole (Cardiff University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports , VOL 32

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 10462 , 14843

Open Access Open Access

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.

Journal Keywords: influenza; CD4 T cells; HLA class II; peptide epitopes; pHLA mutlimer; T cell receptor; clonotypingX-ray crystallography; biochemistry; immunology

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography