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

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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, Flanagan, K, Rossjohn, J, Gras, S, Davies, J, Miller, A, Tong, SYC, Purcell, AW and Kedzierska, K 2021 , 'CD8 + T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph' , Nature Communications, vol. 12, no. 1 , pp. 1-20 , doi: 10.1038/s41467-021-23212-x.

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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.

Item Type: Article
Authors/Creators: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
Journal or Publication Title: Nature Communications
Publisher: Nature Pub. Group
ISSN: 2041-1723
DOI / ID Number: 10.1038/s41467-021-23212-x
Copyright Information:

Copyright 2021 The Authors. Licensed under Creative Common Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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