CD4 + T cells recognize conserved influenza A epitopes through shared patterns of V-Gene usage and complementary biochemical features
Autor: | Robert Andrews, Sarah Nicol Lauder, Aaron Wall, Kathryn Smart, Bruce J. MacLachlan, Meriem Attaf, Pierre J. Rizkallah, Dhanasekaran Vijaykrishna, Yuan Chen, Georgina H. Mason, Andrew James Godkin, Garry Dolton, Mikhail Shugay, David K. Cole, Angharad Lloyd, Cristina Rius, Andrew K. Sewell, Miguel L. Grau, Andrea J. A. Schauenburg, Alexander Greenshields-Watson, Hywel Hughes, Kathryn E. Strange, Awen Gallimore, James Geary, Sarah Hulin-Curtis, Thomas Whalley |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
T cell CD4 T cells chemical and pharmacologic phenomena Human leukocyte antigen Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Epitope 03 medical and health sciences 0302 clinical medicine Immune system medicine Influenza A virus Gene lcsh:QH301-705.5 Genetics T-cell receptor peptide epitopes 030104 developmental biology medicine.anatomical_structure HLA class II lcsh:Biology (General) pHLA mutlimer T cell receptor influenza 030217 neurology & neurosurgery CD8 |
Zdroj: | Cell Reports, Vol 32, Iss 2, Pp 107885-(2020) |
ISSN: | 2211-1247 |
Popis: | 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. |
Databáze: | OpenAIRE |
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