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

Marios Koutsakos¹, Patricia T Illing², Thi H O Nguyen¹, Nicole A Mifsud², Jeremy Chase Crawford³, Simone Rizzetto⁴, Auda A Eltahla⁴, E Bridie Clemens¹, Sneha Sant¹, Brendon Y Chua^{1

5}, Chinn Yi Wong¹, E Kaitlynn Allen³, Don Teng⁶, Pradyot Dash³, David F Boyd³, Ludivine Grzelak^{1

7}, Weiguang Zeng¹, Aeron C Hurt^{1

8}, Ian Barr^{1

8

9}, Steve Rockman^{1

10}, David C Jackson^{1

5}, Tom C Kotsimbos^{11

12}, Allen C Cheng^{13

14}, Michael Richards¹⁵, Glen P Westall¹⁶, Thomas Loudovaris¹⁷, Stuart I Mannering¹⁶, Michael Elliott^{18

19}, Stuart G Tangye^{20

21}, Linda M Wakim¹, Jamie Rossjohn^{2

22

23}, Dhanasekaran Vijaykrishna⁶, Fabio Luciani⁴, Paul G Thomas³, Stephanie Gras^{2

22}, Anthony W Purcell^#², Katherine Kedzierska^#²⁴

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
² Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
³ Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
⁴ School of Medical Sciences and The Kirby Institute, UNSW, Sydney, New South Wales, Australia.
⁵ Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
⁶ Infection and Immunity Program & Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
⁷ Biology Department, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, Cachan, France.
⁸ World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁹ School of Applied Biomedical Sciences, Federation University, Churchill, Victoria, Australia.
¹⁰ Seqirus, Parkville, Victoria, Australia.
¹¹ Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria, Australia.
¹² Department of Medicine, Monash University, Central Clinical School, The Alfred Hospital, Melbourne, Victoria, Australia.
¹³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁴ Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
¹⁶ Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁷ Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
¹⁸ Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
¹⁹ Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
²⁰ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
²¹ St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
²² Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
²³ Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
²⁴ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. kkedz@unimelb.edu.au.

^# Contributed equally.

PMID: 30778243
DOI: 10.1038/s41590-019-0320-6

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

Marios Koutsakos et al. Nat Immunol. 2019 May.

. 2019 May;20(5):613-625.

doi: 10.1038/s41590-019-0320-6. Epub 2019 Feb 18.

Authors

Affiliations

¹ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
² Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
³ Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
⁴ School of Medical Sciences and The Kirby Institute, UNSW, Sydney, New South Wales, Australia.
⁵ Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
⁶ Infection and Immunity Program & Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
⁷ Biology Department, École Normale Supérieure Paris-Saclay, Université Paris-Saclay, Cachan, France.
⁸ World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁹ School of Applied Biomedical Sciences, Federation University, Churchill, Victoria, Australia.
¹⁰ Seqirus, Parkville, Victoria, Australia.
¹¹ Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria, Australia.
¹² Department of Medicine, Monash University, Central Clinical School, The Alfred Hospital, Melbourne, Victoria, Australia.
¹³ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁴ Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
¹⁶ Lung Transplant Unit, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁷ Immunology and Diabetes Unit, St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
¹⁸ Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
¹⁹ Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
²⁰ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
²¹ St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
²² Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
²³ Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
²⁴ Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. kkedz@unimelb.edu.au.

^# Contributed equally.

PMID: 30778243
DOI: 10.1038/s41590-019-0320-6

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.

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References

1. Krammer, F. et al. Influenza. Nat. Rev. Dis. Primers 4, 3 (2018). - DOI
1. Nussing, S. et al. Innate and adaptive T cells in influenza disease. Front. Med. 12, 34–47 (2018). - DOI
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1. Matsuzaki, Y. et al. Clinical features of influenza C virus infection in children. J. Infect. Dis. 193, 1229–1235 (2006). - DOI

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

Affiliations

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

Authors

Affiliations

Abstract

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LinkOut - more resources

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Medical

Research Materials