@article{d46e5d91e4d54ea9b97d710e42e8fde5,
title = "CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph",
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 specificities are present in blood (CD27+CD45RA− phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27−CD45RA−PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.",
author = "Luca Hensen and Illing, {Patricia T.} and {Bridie Clemens}, E. and Nguyen, {Thi H.O.} and Marios Koutsakos and {van de Sandt}, {Carolien E.} and Mifsud, {Nicole A.} and Nguyen, {Andrea T.} and Christopher Szeto and Chua, {Brendon Y.} and Hanim Halim and Simone Rizzetto and Fabio Luciani and Liyen Loh and Grant, {Emma J.} and Saunders, {Phillipa M.} and Brooks, {Andrew G.} and Steve Rockman and Kotsimbos, {Tom C.} and Cheng, {Allen C.} and Michael Richards and Westall, {Glen P.} and Wakim, {Linda M.} and Thomas Loudovaris and Mannering, {Stuart I.} and Michael Elliott and Tangye, {Stuart G.} and Jackson, {David C.} and Flanagan, {Katie L.} and Jamie Rossjohn and Stephanie Gras and Jane Davies and Adrian Miller and Tong, {Steven Y.C.} and Purcell, {Anthony W.} and Katherine Kedzierska",
note = "Funding Information: HHD-A24 transgenic HHD mice were developed by Dr. Francoi{\c s} 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{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-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). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = may,
day = "18",
doi = "10.1038/s41467-021-23212-x",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}