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Nat Immunol. 2019 May;20(5):613-625. doi: 10.1038/s41590-019-0320-6. Epub 2019 Feb 18.

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

Author information

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.

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
[Indexed for MEDLINE]

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