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Nat. Immun. Human CD8+ T cell cross-reactivity across influenza A, B and C viruses

tetano

Editor, Senior Moderator
Nat Immunol. 2019 Feb 18. doi: 10.1038/s41590-019-0320-6. [Epub ahead of print]
[h=1]Human CD8[SUP]+[/SUP] T cell cross-reactivity across influenza A, B and C viruses.[/h] Koutsakos M[SUP]1[/SUP], Illing PT[SUP]2[/SUP], Nguyen THO[SUP]1[/SUP], Mifsud NA[SUP]2[/SUP], Crawford JC[SUP]3[/SUP], Rizzetto S[SUP]4[/SUP], Eltahla AA[SUP]4[/SUP], Clemens EB[SUP]1[/SUP], Sant S[SUP]1[/SUP], Chua BY[SUP]1,[/SUP][SUP]5[/SUP], Wong CY[SUP]1[/SUP], Allen EK[SUP]3[/SUP], Teng D[SUP]6[/SUP], Dash P[SUP]3[/SUP], Boyd DF[SUP]3[/SUP], Grzelak L[SUP]1,[/SUP][SUP]7[/SUP], Zeng W[SUP]1[/SUP], Hurt AC[SUP]1,[/SUP][SUP]8[/SUP], Barr I[SUP]1,[/SUP][SUP]8,[/SUP][SUP]9[/SUP], Rockman S[SUP]1,[/SUP][SUP]10[/SUP], Jackson DC[SUP]1,[/SUP][SUP]5[/SUP], Kotsimbos TC[SUP]11,[/SUP][SUP]12[/SUP], Cheng AC[SUP]13,[/SUP][SUP]14[/SUP], Richards M[SUP]15[/SUP], Westall GP[SUP]16[/SUP], Loudovaris T[SUP]17[/SUP], Mannering SI[SUP]16[/SUP], Elliott M[SUP]18,[/SUP][SUP]19[/SUP], Tangye SG[SUP]20,[/SUP][SUP]21[/SUP], Wakim LM[SUP]1[/SUP], Rossjohn J[SUP]2,[/SUP][SUP]22,[/SUP][SUP]23[/SUP], Vijaykrishna D[SUP]6[/SUP], Luciani F[SUP]4[/SUP], Thomas PG[SUP]3[/SUP], Gras S[SUP]2,[/SUP][SUP]22[/SUP], Purcell AW[SUP]2[/SUP], Kedzierska K[SUP]24[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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[SUP]+[/SUP] T cells confer cross-protection against IAV strains, however the responses of CD8[SUP]+[/SUP] T cells to IBV and ICV are understudied. We investigated the breadth of CD8[SUP]+[/SUP] T cell cross-recognition and provide evidence of CD8[SUP]+[/SUP] T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8[SUP]+[/SUP] T cell epitopes from IBVs that were protective in mice and found memory CD8[SUP]+[/SUP] T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8[SUP]+[/SUP] T cells displayed tissue-resident memory phenotypes. Notably, CD38[SUP]+[/SUP]Ki67[SUP]+[/SUP]CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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
 
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