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

Emma J. Grant, Tracy M. Josephs, Liyen Loh, E. Bridie Clemens, Sneha Sant, Mandvi Bharadwaj, Weisan Chen, Jamie Rossjohn, Stephanie Gras, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Article number5427
Number of pages16
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 21 Dec 2018

Keywords

  • immunological memory
  • influenza virus
  • translational immunology
  • x-ray crystallography

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