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

• DOI: 10.1038/s41467-021-23212-x
• Publication Date: 2021-05-18T10:04:35Z
• Authors: Luca Hensen; Patricia T. Illing; E. Bridie Clemens; Thi H. O. Nguyen; Marios Koutsakos; Carolien E. van d...; Nicole A. Mifsud; Andrea T. Nguyen; Christopher Szeto; Brendon Y. Chua; Hanim Halim; Simone Rizzetto; Fabio Luciani; Liyen Loh; Emma J. Grant; Phillipa M. Saunders; Andrew G. Brooks; Steve Rockman; Tom C. Kotsimbos; Allen C. Cheng; Michael Richards; Glen P. Westall; Linda M. Wakim; Thomas Loudovaris; Stuart I. Mannering; Michael Elliott; Stuart G. Tangye; David C. Jackson; Katie L. Flanagan; Jamie Rossjohn; Stephanie Gras; Jane Davies; Adrian Miller; Steven Y. C. Tong; Anthony W. Purcell; Katherine Kedzierska
• Keywords: Adult; Male; 0301 basic medicine; Science; 610; Epitopes, T-Lymphocyte; HLA-A24 Antigen; Mice, Transgenic; CD8-Positive T-Lymphocytes; Article; 03 medical and health sciences; Dogs; Gene Frequency; 616; Influenza, Human; Animals; Humans; Amino Acid Sequence; Indigenous Peoples; Alleles; Cells, Cultured; Uncategorized; 0303 health sciences; Q; Australia; Middle Aged; 15. Life on land; 3. Good health; Influenza B virus; Influenza A virus; Female

Abstract Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in populations, is associated with influenza-induced mortality, although the basis for this association unclear. Here, we define CD8 + T-cell immune landscapes against A (IAV) and B (IBV) viruses HLA-A*24:02-expressing non-Indigenous individuals, human tissues, influenza-infected patients HLA-A*24:02-transgenic mice. We identify immunodominant protective epitopes, one towards IAV six IBV, A24/PB2 550–558 -specific T cells being cross-reactive between IBV. Memory these specificities present blood (CD27 CD45RA − phenotype) tissues (CD103 CD69 healthy effector CD27 PD-1 CD38 IAV/IBV patients. Our data show influenza-specific responses Australians, advocate T-cell-mediated vaccines that target boost breadth IAV/IBV-specific to protect high-risk populations from