Journal article

CD8( ) T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Luca Hensen, Patricia T Illing, E Bridie Clemens, Thi HO Nguyen, Marios Koutsakos, Carolien E van de Sandt, Nicole A Mifsud, Andrea T Nguyen, Christopher Szeto, Brendon Y Chua, Hanim Halim, Simone Rizzetto, Fabio Luciani, Liyen Loh, Emma J Grant, Phillipa M Saunders, Andrew G Brooks, Steve Rockman, Tom C Kotsimbos, Allen C Cheng Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

Abstract

Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550-558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC) Program Grant


Awarded by NHMRC


Awarded by NIAID UO1 grant


Awarded by ARC


Awarded by European Union


Awarded by NHMRC SRF-A Fellow


Funding Acknowledgements

HHD-A24 transgenic HHD mice were developed by Dr. Francois Lemonnier (Pasteur Institute, Paris, France). We thank the Monash Macromolecular Crystallization Facility staff and the staff at the Australian synchrotron for technical assistance. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. The Australian National Health and Medical Research Council (NHMRC) Program Grant (#1071916) to K.K., NHMRC Project Grant (#1122524) to K.K., S.T., A.M., S.G., and A.W.P., and NHMRC Investigator Grant (#1173871) to K.K. supported this work. This work was also supported by NIAID UO1 grant 1U01AI144616-01; Dissection of Influenza Vaccination and Infection for Childhood Immunity (DIVINCI) to K.K. and by the ARC grant # DP190103282 to K.K., A.G.B., and L.L. L.H. was a recipient of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. C.E.S. had received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant agreement (#792532). J.R. is supported by an ARC Laureate fellowship. S.G. is an NHMRC SRF-A Fellow (#1159272). E.B.C. is NHMRC Peter Doherty Fellow. A.W.P. is supported by an NHMRC Principal Research Fellowship (#1137739) and NHMRC Project grant (#1085018) to A.W.P., N.A.M., and T.C.K. S.T. is an NHMRC Career Development Fellow (#1145033). E.J.G. is an NHMRC CJ Martin Fellow. P.T.I. was supported by an NHMRC Early Career Fellowship (#1072159) and Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship (2020).