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


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 (TCR??) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCR?? 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 TCR?? 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.

SUBMITTER: Grant EJ 

PROVIDER: S-EPMC6303473 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Grant Emma J EJ   Josephs Tracy M TM   Loh Liyen L   Clemens E Bridie EB   Sant Sneha S   Bharadwaj Mandvi M   Chen Weisan W   Rossjohn Jamie J   Gras Stephanie S   Kedzierska Katherine K  

Nature communications 20181221 1


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<sup>+</sup> 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 varian  ...[more]

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