tetano
Editor, Senior Moderator
Nat Commun
. 2021 May 18;12(1):2931.
doi: 10.1038/s41467-021-23212-x.
CD8 [SUP]+[/SUP] T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
Luca Hensen[SUP] #[/SUP][SUP] 1 [/SUP], Patricia T Illing[SUP] #[/SUP][SUP] 2 [/SUP], E Bridie Clemens[SUP] #[/SUP][SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Carolien E van de Sandt[SUP] 1 3 [/SUP], Nicole A Mifsud[SUP] 2 [/SUP], Andrea T Nguyen[SUP] 2 [/SUP], Christopher Szeto[SUP] 2 [/SUP], Brendon Y Chua[SUP] 1 [/SUP], Hanim Halim[SUP] 2 [/SUP], Simone Rizzetto[SUP] 4 [/SUP], Fabio Luciani[SUP] 4 [/SUP], Liyen Loh[SUP] 1 [/SUP], Emma J Grant[SUP] 1 2 [/SUP], Phillipa M Saunders[SUP] 1 [/SUP], Andrew G Brooks[SUP] 1 [/SUP], Steve Rockman[SUP] 1 5 [/SUP], Tom C Kotsimbos[SUP] 6 7 [/SUP], Allen C Cheng[SUP] 8 9 [/SUP], Michael Richards[SUP] 10 [/SUP], Glen P Westall[SUP] 11 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Thomas Loudovaris[SUP] 12 [/SUP], Stuart I Mannering[SUP] 12 [/SUP], Michael Elliott[SUP] 13 14 [/SUP], Stuart G Tangye[SUP] 15 16 [/SUP], David C Jackson[SUP] 1 [/SUP], Katie L Flanagan[SUP] 17 18 19 20 [/SUP], Jamie Rossjohn[SUP] 2 21 22 [/SUP], Stephanie Gras[SUP] 2 22 23 [/SUP], Jane Davies[SUP] 24 [/SUP], Adrian Miller[SUP] 25 [/SUP], Steven Y C Tong[SUP] 10 24 [/SUP], Anthony W Purcell[SUP] 2 [/SUP], Katherine Kedzierska[SUP] 26 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP] T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2[SUB]550-558[/SUB]-specific CD8[SUP]+[/SUP] T cells being cross-reactive between IAV and IBV. Memory CD8[SUP]+[/SUP] T cells towards these specificities are present in blood (CD27[SUP]+[/SUP]CD45RA[SUP]-[/SUP] phenotype) and tissues (CD103[SUP]+[/SUP]CD69[SUP]+[/SUP] phenotype) of healthy individuals, and effector CD27[SUP]-[/SUP]CD45RA[SUP]-[/SUP]PD-1[SUP]+[/SUP]CD38[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells in IAV/IBV patients. Our data show influenza-specific CD8[SUP]+[/SUP] T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8[SUP]+[/SUP] T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.
. 2021 May 18;12(1):2931.
doi: 10.1038/s41467-021-23212-x.
CD8 [SUP]+[/SUP] T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph
Luca Hensen[SUP] #[/SUP][SUP] 1 [/SUP], Patricia T Illing[SUP] #[/SUP][SUP] 2 [/SUP], E Bridie Clemens[SUP] #[/SUP][SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Marios Koutsakos[SUP] 1 [/SUP], Carolien E van de Sandt[SUP] 1 3 [/SUP], Nicole A Mifsud[SUP] 2 [/SUP], Andrea T Nguyen[SUP] 2 [/SUP], Christopher Szeto[SUP] 2 [/SUP], Brendon Y Chua[SUP] 1 [/SUP], Hanim Halim[SUP] 2 [/SUP], Simone Rizzetto[SUP] 4 [/SUP], Fabio Luciani[SUP] 4 [/SUP], Liyen Loh[SUP] 1 [/SUP], Emma J Grant[SUP] 1 2 [/SUP], Phillipa M Saunders[SUP] 1 [/SUP], Andrew G Brooks[SUP] 1 [/SUP], Steve Rockman[SUP] 1 5 [/SUP], Tom C Kotsimbos[SUP] 6 7 [/SUP], Allen C Cheng[SUP] 8 9 [/SUP], Michael Richards[SUP] 10 [/SUP], Glen P Westall[SUP] 11 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Thomas Loudovaris[SUP] 12 [/SUP], Stuart I Mannering[SUP] 12 [/SUP], Michael Elliott[SUP] 13 14 [/SUP], Stuart G Tangye[SUP] 15 16 [/SUP], David C Jackson[SUP] 1 [/SUP], Katie L Flanagan[SUP] 17 18 19 20 [/SUP], Jamie Rossjohn[SUP] 2 21 22 [/SUP], Stephanie Gras[SUP] 2 22 23 [/SUP], Jane Davies[SUP] 24 [/SUP], Adrian Miller[SUP] 25 [/SUP], Steven Y C Tong[SUP] 10 24 [/SUP], Anthony W Purcell[SUP] 2 [/SUP], Katherine Kedzierska[SUP] 26 [/SUP]
Affiliations
- PMID: 34006841
- DOI: 10.1038/s41467-021-23212-x
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[SUP]+[/SUP] 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[SUP]+[/SUP] T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2[SUB]550-558[/SUB]-specific CD8[SUP]+[/SUP] T cells being cross-reactive between IAV and IBV. Memory CD8[SUP]+[/SUP] T cells towards these specificities are present in blood (CD27[SUP]+[/SUP]CD45RA[SUP]-[/SUP] phenotype) and tissues (CD103[SUP]+[/SUP]CD69[SUP]+[/SUP] phenotype) of healthy individuals, and effector CD27[SUP]-[/SUP]CD45RA[SUP]-[/SUP]PD-1[SUP]+[/SUP]CD38[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells in IAV/IBV patients. Our data show influenza-specific CD8[SUP]+[/SUP] T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8[SUP]+[/SUP] T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.