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Nat Commun. 2018 Dec 21;9(1):5427. doi: 10.1038/s41467-018-07815-5.

Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans.

Author information

1
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3010, Australia.
2
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
3
Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Bundoora, 3084, VIC, Australia.
4
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
5
ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia.
6
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. stephanie.gras@monash.edu.
7
ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, 3800, Australia. stephanie.gras@monash.edu.
8
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3010, Australia. kkedz@unimelb.edu.au.

Abstract

Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+ T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+ T-cell-targeted vaccines could provide protection across different IAV strains.

PMID:
30575715
PMCID:
PMC6303473
DOI:
10.1038/s41467-018-07815-5
[Indexed for MEDLINE]
Free PMC Article

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