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Human CD8(+) T cell cross-reactivity across influenza A, B and C viruses


Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8(+) T cells confer cross-protection against IAV strains, however the responses of CD8(+) T cells to IBV and ICV are understudied. We investigated the breadth of CD8(+) T cell cross-recognition and provide evidence of CD8(+) T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8(+) T cell epitopes from IBVs that were protective in mice and found memory CD8(+) T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8(+) T cells displayed tissue-resident memory phenotypes. Notably, CD38(+)Ki67(+)CD8(+) effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8(+) T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines.

Type Journal
ISBN 1529-2916 (Electronic) 1529-2908 (Linking)
Authors Koutsakos, M.; Illing, P. T.; Nguyen, T. H. O.; Mifsud, N. A.; Crawford, J. C.; Rizzetto, S.; Eltahla, A. A.; Clemens, E. B.; Sant, S.; Chua, B. Y.; Wong, C. Y.; Allen, E. K.; Teng, D.; Dash, P.; Boyd, D. F.; Grzelak, L.; Zeng, W.; Hurt, A. C.; Barr, I.; Rockman, S.; Jackson, D. C.; Kotsimbos, T. C.; Cheng, A. C.; Richards, M.; Westall, G. P.; Loudovaris, T.; Mannering, S. I.; Elliott, M.; Tangye, S. G.; Wakim, L. M.; Rossjohn, J.; Vijaykrishna, D.; Luciani, F.; Thomas, P. G.; Gras, S.; Purcell, A. W.; Kedzierska, K.
Responsible Garvan Author Prof Stuart Tangye
Published Date 2019-05-01
Published Volume 20
Published Issue 5
Published Pages 613-625
Status Published in-print
DOI 10.1038/s41590-019-0320-6
URL link to publisher's version