Journal article
Human CD8( ) T cell cross-reactivity across influenza A, B and C viruses
Marios Koutsakos, Patricia T Illing, Thi HO 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 Show all
NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2019
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..
View full abstractRelated Projects (2)
Grants
Awarded by Australian National Health and Medical Research Council (NHMRC) NHMRC Program Grant
Awarded by NHMRC principal research fellowship
Awarded by NHMRC project grant
Awarded by US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services
Awarded by NHMRC Peter Doherty fellowship
Awarded by St. Jude Center of Excellence for Influenza Research and Surveillance (NIAID)
Awarded by JDRF Career Development award
Awarded by NHMRC Project
Funding Acknowledgements
HLA-A2.1 transgenic HHD mice were developed by F. Lemonnier (Pasteur Institute). D227K and Q115E MHC-I constructs were developed and provided by L. Wooldridge (Bristol University). The authors acknowledge the provision of instrumentation, training and technical support by the Monash Biomedical Proteomics Facility. We thank all study participants and organ donors. We are grateful to the coordinators of DonateLife Victoria for obtaining organ tissues, and to L. Mariana and C. Kos (St. Vincent's Institute) for their assistance. The Australian National Health and Medical Research Council (NHMRC) NHMRC Program Grant (1071916) to K.K. supported this work. M.K. is a recipient of a Melbourne International research scholarship and Melbourne International fee remission scholarship. S.S. is a recipient of a Victoria India doctoral scholarship and Melbourne International fee remission scholarship, University of Melbourne. K.K. is an NHMRC senior research level B fellow (1102792). J.R. is supported by an ARC laureate fellowship. S.G. is a Monash senior research fellow. F.L. and A.C.C. are NHMRC CDF2 fellows. E.B.C. and A.A.E. are NHMRC Peter Doherty fellows. The Melbourne WHO Collaborating Centre for Reference Research on Influenza is supported by the Australian Government Department of Health. A.W.P. is supported by an NHMRC principal research fellowship (1137739) and an NHMRC project grant (1085018) to A.W.P., T.C.K. and N.A.M. D.T. and D.V. are supported by contract HHSN272201400006C from the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services. P.T.I. was supported by a NHMRC Peter Doherty fellowship (1072159). P.G.T. is supported by the St. Jude Center of Excellence for Influenza Research and Surveillance (NIAID contract HHSN27220140006C), R01AI107625, R01AI136514, and American Lebanese Syrian Associated Charities. S.I.M. is supported by a JDRF Career Development award (5-CDA2014210-A-N) and NHMRC Project (GNT 1123586).