Publication
Article Metrics
Citations
Online attention
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
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
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
Diamond Keywords: Influenza; Viruses
Subject Areas:
Biology and Bio-materials,
Chemistry,
Medicine
Instruments:
I03-Macromolecular Crystallography
,
I04-Macromolecular Crystallography
Added On:
15/07/2020 08:47
Documents:
1-s2.0-S2211124720308664-main.pdf
Discipline Tags:
Vaccines
Pathogens
Infectious Diseases
Health & Wellbeing
Biochemistry
Genetics
Chemistry
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags: