1165819_Hensen,L_2021.pdf (7.96 MB)
Download fileCD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
journal contribution
posted on 2021-07-06, 06:37 authored by L Hensen, PT Illing, E Bridie Clemens, THO Nguyen, M Koutsakos, CE van de Sandt, NA Mifsud, Andrea NguyenAndrea Nguyen, Christopher SzetoChristopher Szeto, BY Chua, H Halim, S Rizzetto, F Luciani, L Loh, Emma GrantEmma 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, KL Flanagan, J Rossjohn, Stephanie GrasStephanie Gras, J Davies, A Miller, SYC Tong, AW Purcell, K KedzierskaIndigenous 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/PB2 -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.
