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

Cell Reports
Alexander Greenshields-WatsonDavid K Cole

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.

Citations

Dec 31, 2020·International Journal of Molecular Sciences·Demetra S M ChatzileontiadouEmma J Grant

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Methods Mentioned

BETA
flow cytometry
X-ray
transgenic
clonotyping
FCS
column chromatography
size exclusion column chromatography
flow
FACS
PCR

Software Mentioned

PyMOL
REFMAC5
gridextra
MUSCLE
RAxML
CCP4i2
ggseqlogo
R package ‘ muscle
xia
NetMHCIIpan

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