146433 - CD8 T cell landscape.pdf (7.96 MB)
CD8 + T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
journal contribution
posted on 2023-05-21, 02:14 authored by Hensen, L, Illing, PT, Bridie Clemens, E, Nguyen, THO, Koutsakos, M, van de Sandt, CE, Mifsud, NA, Nguyen, AT, Szeto, C, Chua, BY, Halim, H, Rizzetto, S, Luciani, F, Loh, L, Grant, EJ, Saunders, PM, Brooks, AG, Rockman, S, Kotsimbos, TC, Cheng, AC, Richards, M, Westall, GP, Wakim, LM, Loudovaris, T, Mannering, SI, Elliott, M, Tangye, SG, Jackson, DC, Katie FlanaganKatie Flanagan, Rossjohn, J, Gras, S, Davies, J, Miller, A, Tong, SYC, Purcell, AW, Kedzierska, KIndigenous 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 CommunicationsVolume
12Article number
2931Number
2931Pagination
1-20ISSN
2041-1723Department/School
Tasmanian School of MedicinePublisher
Nature Pub. GroupPlace of publication
United KingdomRights statement
Copyright 2021 The Authors. Licensed under Creative Common Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open