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

Marios Koutsakos, Patricia T. Illing, Thi H.O. Nguyen, Nicole A. Mifsud, Jeremy Chase Crawford, Simone Rizzetto, Auda A. Eltahla, E. Bridie Clemens, Sneha Sant, Brendon Y. Chua, Chinn Yi Wong, E. Kaitlynn Allen, Don Teng, Pradyot Dash, David F. Boyd, Ludivine Grzelak, Weiguang Zeng, Aeron C. Hurt, Ian Barr, Steve Rockman & 17 others David C. Jackson, Tom C. Kotsimbos, Allen C. Cheng, Michael Richards, Glen P. Westall, Thomas Loudovaris, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, Linda M. Wakim, Jamie Rossjohn, Dhanasekaran Vijaykrishna, Fabio Luciani, Paul G. Thomas, Stephanie Gras, Anthony W. Purcell, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)613-625
Number of pages15
JournalNature Immunology
Volume20
DOIs
Publication statusPublished - 18 Feb 2019

Cite this

Koutsakos, M., Illing, P. T., Nguyen, T. H. O., Mifsud, N. A., Crawford, J. C., Rizzetto, S., ... Kedzierska, K. (2019). Human CD8 + T cell cross-reactivity across influenza A, B and C viruses. Nature Immunology, 20, 613-625. https://doi.org/10.1038/s41590-019-0320-6
Koutsakos, Marios ; Illing, Patricia T. ; Nguyen, Thi H.O. ; Mifsud, Nicole A. ; Crawford, Jeremy Chase ; Rizzetto, Simone ; Eltahla, Auda A. ; Clemens, E. Bridie ; Sant, Sneha ; Chua, Brendon Y. ; Wong, Chinn Yi ; Allen, E. Kaitlynn ; Teng, Don ; Dash, Pradyot ; Boyd, David F. ; Grzelak, Ludivine ; Zeng, Weiguang ; Hurt, Aeron C. ; Barr, Ian ; Rockman, Steve ; Jackson, David C. ; Kotsimbos, Tom C. ; Cheng, Allen C. ; Richards, Michael ; Westall, Glen P. ; Loudovaris, Thomas ; Mannering, Stuart I. ; Elliott, Michael ; Tangye, Stuart G. ; Wakim, Linda M. ; Rossjohn, Jamie ; Vijaykrishna, Dhanasekaran ; Luciani, Fabio ; Thomas, Paul G. ; Gras, Stephanie ; Purcell, Anthony W. ; Kedzierska, Katherine. / Human CD8 + T cell cross-reactivity across influenza A, B and C viruses. In: Nature Immunology. 2019 ; Vol. 20. pp. 613-625.
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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.",
author = "Marios Koutsakos and Illing, {Patricia T.} and Nguyen, {Thi H.O.} and Mifsud, {Nicole A.} and Crawford, {Jeremy Chase} and Simone Rizzetto and Eltahla, {Auda A.} and Clemens, {E. Bridie} and Sneha Sant and Chua, {Brendon Y.} and Wong, {Chinn Yi} and Allen, {E. Kaitlynn} and Don Teng and Pradyot Dash and Boyd, {David F.} and Ludivine Grzelak and Weiguang Zeng and Hurt, {Aeron C.} and Ian Barr and Steve Rockman and Jackson, {David C.} and Kotsimbos, {Tom C.} and Cheng, {Allen C.} and Michael Richards and Westall, {Glen P.} and Thomas Loudovaris and Mannering, {Stuart I.} and Michael Elliott and Tangye, {Stuart G.} and Wakim, {Linda M.} and Jamie Rossjohn and Dhanasekaran Vijaykrishna and Fabio Luciani and Thomas, {Paul G.} and Stephanie Gras and Purcell, {Anthony W.} and Katherine Kedzierska",
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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, W, 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 2019, 'Human CD8 + T cell cross-reactivity across influenza A, B and C viruses', Nature Immunology, vol. 20, pp. 613-625. https://doi.org/10.1038/s41590-019-0320-6

Human CD8 + T cell cross-reactivity across influenza A, B and C viruses. / Koutsakos, Marios; Illing, Patricia T.; Nguyen, Thi H.O.; Mifsud, Nicole A.; Crawford, Jeremy Chase; Rizzetto, Simone; Eltahla, Auda A.; Clemens, E. Bridie; Sant, Sneha; Chua, Brendon Y.; Wong, Chinn Yi; Allen, E. Kaitlynn; Teng, Don; Dash, Pradyot; Boyd, David F.; Grzelak, Ludivine; Zeng, Weiguang; Hurt, Aeron C.; Barr, Ian; Rockman, Steve; Jackson, David C.; Kotsimbos, Tom C.; Cheng, Allen C.; Richards, Michael; Westall, Glen P.; Loudovaris, Thomas; Mannering, Stuart I.; Elliott, Michael; Tangye, Stuart G.; Wakim, Linda M.; Rossjohn, Jamie; Vijaykrishna, Dhanasekaran; Luciani, Fabio; Thomas, Paul G.; Gras, Stephanie; Purcell, Anthony W.; Kedzierska, Katherine.

In: Nature Immunology, Vol. 20, 18.02.2019, p. 613-625.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human CD8 + T cell cross-reactivity across influenza A, B and C viruses

AU - Koutsakos, Marios

AU - Illing, Patricia T.

AU - Nguyen, Thi H.O.

AU - Mifsud, Nicole A.

AU - Crawford, Jeremy Chase

AU - Rizzetto, Simone

AU - Eltahla, Auda A.

AU - Clemens, E. Bridie

AU - Sant, Sneha

AU - Chua, Brendon Y.

AU - Wong, Chinn Yi

AU - Allen, E. Kaitlynn

AU - Teng, Don

AU - Dash, Pradyot

AU - Boyd, David F.

AU - Grzelak, Ludivine

AU - Zeng, Weiguang

AU - Hurt, Aeron C.

AU - Barr, Ian

AU - Rockman, Steve

AU - Jackson, David C.

AU - Kotsimbos, Tom C.

AU - Cheng, Allen C.

AU - Richards, Michael

AU - Westall, Glen P.

AU - Loudovaris, Thomas

AU - Mannering, Stuart I.

AU - Elliott, Michael

AU - Tangye, Stuart G.

AU - Wakim, Linda M.

AU - Rossjohn, Jamie

AU - Vijaykrishna, Dhanasekaran

AU - Luciani, Fabio

AU - Thomas, Paul G.

AU - Gras, Stephanie

AU - Purcell, Anthony W.

AU - Kedzierska, Katherine

PY - 2019/2/18

Y1 - 2019/2/18

N2 - 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.

AB - 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.

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U2 - 10.1038/s41590-019-0320-6

DO - 10.1038/s41590-019-0320-6

M3 - Article

VL - 20

SP - 613

EP - 625

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

ER -