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Publication Abstract from PubMed

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/PB2(550-558)-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.

CD8(+) T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph.,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 KL, Rossjohn J, Gras S, Davies J, Miller A, Tong SYC, Purcell AW, Kedzierska K Nat Commun. 2021 May 18;12(1):2931. doi: 10.1038/s41467-021-23212-x. PMID:34006841^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.