Nat Immunol. 2019 Feb 18. doi: 10.1038/s41590-019-0320-6. [Epub ahead of print]
Human CD8+ T cell cross-reactivity across influenza A, B and C viruses.
Koutsakos M1, Illing PT2, Nguyen THO1, Mifsud NA2, Crawford JC3, Rizzetto S4, Eltahla AA4, Clemens EB1, Sant S1, Chua BY1,5, Wong CY1, Allen EK3, Teng D6, Dash P3, Boyd DF3, Grzelak L1,7, Zeng W1, Hurt AC1,8, Barr I1,8,9, Rockman S1,10, Jackson DC1,5, Kotsimbos TC11,12, Cheng AC13,14, Richards M15, Westall GP16, Loudovaris T17, Mannering SI16, Elliott M18,19, Tangye SG20,21, Wakim LM1, Rossjohn J2,22,23, Vijaykrishna D6, Luciani F4, Thomas PG3, Gras S2,22, Purcell AW2, Kedzierska K24.
Author information
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.
PMID: 30778243 DOI: 10.1038/s41590-019-0320-6
Human CD8+ T cell cross-reactivity across influenza A, B and C viruses.
Koutsakos M1, Illing PT2, Nguyen THO1, Mifsud NA2, Crawford JC3, Rizzetto S4, Eltahla AA4, Clemens EB1, Sant S1, Chua BY1,5, Wong CY1, Allen EK3, Teng D6, Dash P3, Boyd DF3, Grzelak L1,7, Zeng W1, Hurt AC1,8, Barr I1,8,9, Rockman S1,10, Jackson DC1,5, Kotsimbos TC11,12, Cheng AC13,14, Richards M15, Westall GP16, Loudovaris T17, Mannering SI16, Elliott M18,19, Tangye SG20,21, Wakim LM1, Rossjohn J2,22,23, Vijaykrishna D6, Luciani F4, Thomas PG3, Gras S2,22, Purcell AW2, Kedzierska K24.
Author information
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.
PMID: 30778243 DOI: 10.1038/s41590-019-0320-6