Title: Human CD8(+) T cell cross-reactivity across influenza A, B and C viruses
Authors: Koutsakos, M
Illing, PT
Nguyen, THO
Mifsud, NA
Crawford, JC
Rizzetto, S
Eltahla, AA
Clemens, EB
Sant, S
Chua, BY
Wong, CY
Allen, EK
Teng, D
Dash, P
Boyd, DF
Grzelak, L
Zeng, WG
Hurt, AC
Barr, I
Rockman, S
Jackson, DC
Kotsimbos, TC
Cheng, AC
Richards, M
Westall, GP
Loudovaris, T
Mannering, SI
Elliott, M
Tangye, SG
Wakim, LM
Rossjohn, J
Vijaykrishna, D
Luciani, F
Thomas, PG
Gras, S
Purcell, AW
Kedzierska, K
Issue Year: 2019
Series Nat. Immunol.:
Abstract 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.
URI: https://publications.svi.edu.au/publications/2496
Other Identifiers 10.1038/s41590-019-0320-6
Publication type Article