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


Hensen, L and Illing, PT and Bridie Clemens, E and Nguyen, THO and Koutsakos, M and van de Sandt, CE and Mifsud, NA and Nguyen, AT and Szeto, C and Chua, BY and Halim, H and Rizzetto, S and Luciani, F and Loh, L and Grant, EJ and Saunders, PM and Brooks, AG and Rockman, S and Kotsimbos, TC and Cheng, AC and Richards, M and Westall, GP and Wakim, LM and Loudovaris, T and Mannering, SI and Elliott, M and Tangye, SG and Jackson, DC and Flanagan, K and Rossjohn, J and Gras, S and Davies, J and Miller, A and Tong, SYC and Purcell, AW and Kedzierska, K, CD8 + T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph, Nature Communications, 12, (1) Article 2931. ISSN 2041-1723 (2021) [Refereed Article]


Copyright Statement

Copyright 2021 The Authors. Licensed under Creative Common Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/s41467-021-23212-x


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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Microbiology
Research Field:Virology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Flanagan, K (Dr Katie Flanagan)
ID Code:146433
Year Published:2021
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-09-07
Last Modified:2022-12-06
Downloads:10 View Download Statistics

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