Author: Hensen, Luca; Illing, Patricia T; Bridie Clemens, E; Nguyen, Thi H O; Koutsakos, Marios; van de Sandt, Carolien E; Mifsud, Nicole A; Nguyen, Andrea T; Szeto, Christopher; Chua, Brendon Y; Halim, Hanim; Rizzetto, Simone; Luciani, Fabio; Loh, Liyen; Grant, Emma J; Saunders, Phillipa M; Brooks, Andrew G; Rockman, Steve; Kotsimbos, Tom C; Cheng, Allen C; Richards, Michael; Westall, Glen P; Wakim, Linda M; Loudovaris, Thomas; Mannering, Stuart I; Elliott, Michael; Tangye, Stuart G; Jackson, David C; Flanagan, Katie L; Rossjohn, Jamie; Gras, Stephanie; Davies, Jane; Miller, Adrian; Tong, Steven Y C; Purcell, Anthony W; Kedzierska, Katherine
Title: CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph. Cord-id: iqpf8q4q Document date: 2021_5_18
ID: iqpf8q4q
Snippet: 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 im
Document: 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.
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