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， CD38Ki67CD8 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.