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journal contribution
posted on 2024-11-21, 01:04authored byL Hensen, PT Illing, E Bridie Clemens, THO Nguyen, M Koutsakos, CE van de Sandt, NA Mifsud, AT Nguyen, C Szeto, BY Chua, H Halim, S Rizzetto, F Luciani, L Loh, EJ Grant, PM Saunders, AG Brooks, S Rockman, TC Kotsimbos, AC Cheng, M Richards, GP Westall, LM Wakim, T Loudovaris, SI Mannering, M Elliott, SG Tangye, DC Jackson, Katie FlanaganKatie Flanagan, J Rossjohn, S Gras, J Davies, A Miller, SYC Tong, AW Purcell, K Kedzierska
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.
History
Publication title
Nature Communications
Volume
12
Issue
1
Article number
2931
Number
2931
Pagination
1-20
ISSN
2041-1723
Department/School
Medicine
Publisher
Nature Pub. Group
Publication status
Published
Place of publication
United Kingdom
Rights statement
Copyright 2021 The Authors. Licensed under Creative Common Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Socio-economic Objectives
200105 Treatment of human diseases and conditions, 210302 Aboriginal and Torres Strait Islander health status and outcomes