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

Grant, Emma J., Josephs, Tracy M., Loh, Liyen, Clemens, E. Bridie, Sant, Sneha, Bharadwaj, Mandvi, Chen, Weisan, Rossjohn, Jamie, Gras, Stephanie and Kedzierska, Katherine 2018. Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans. Nature Communications 9 (1) , -. 10.1038/s41467-018-07815-5

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 10 January 2019
Date of Acceptance: 23 November 2018
Last Modified: 12 Jun 2019 02:16
URI: http://orca.cf.ac.uk/id/eprint/118288

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