| 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 |
| Publisher | NATURE PUBLISHING GROUP |
| 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 |