6mt5

Publication Abstract from PubMed

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

Broad CD8(+) T cell cross-recognition of distinct influenza A strains in humans.,Grant EJ, Josephs TM, Loh L, Clemens EB, Sant S, Bharadwaj M, Chen W, Rossjohn J, Gras S, Kedzierska K Nat Commun. 2018 Dec 21;9(1):5427. doi: 10.1038/s41467-018-07815-5. PMID:30575715^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.