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Nat Commun . CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Apr 29;15(1):3387.
doi: 10.1038/s41467-024-47576-y. CD8[SUP]+[/SUP] T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age

Tejas Menon[SUP] #[/SUP][SUP] 1 [/SUP], Patricia T Illing[SUP] #[/SUP][SUP] 2 [/SUP], Priyanka Chaurasia[SUP] #[/SUP][SUP] 2 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Chloe Shepherd[SUP] 2 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Jan Petersen[SUP] 2 [/SUP], Dene R Littler[SUP] 2 [/SUP], Grace Khuu[SUP] 2 [/SUP], Ziyi Huang[SUP] 2 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Steve Rockman[SUP] 1 3 [/SUP], Jane Crowe[SUP] 4 [/SUP], Katie L Flanagan[SUP] 5 6 7 [/SUP], Linda M Wakim[SUP] 1 [/SUP], Thi H O Nguyen[SUP] 1 [/SUP], Nicole A Mifsud[SUP] 2 [/SUP], Jamie Rossjohn[SUP] 2 8 [/SUP], Anthony W Purcell[SUP] 2 [/SUP], Carolien E van de Sandt[SUP] 1 9 [/SUP], Katherine Kedzierska[SUP] 10 [/SUP]



Affiliations
Abstract

Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8[SUP]+[/SUP] T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8[SUP]+[/SUP] T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer[SUP]+[/SUP]CD8[SUP]+[/SUP] T-cells are present within blood and tissues. Frequencies of IBV-specific CD8[SUP]+[/SUP] T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP[SUB]30-38[/SUB] epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1[SUB]196-206[/SUB] (11-mer) and HLA-B*07:02-restricted NP[SUB]30-38[/SUB] epitope presentation. Our study increases the number of IBV CD8[SUP]+[/SUP] T-cell epitopes, and defines IBV-specific CD8[SUP]+[/SUP] T-cells at cellular and molecular levels, across tissues and age.


 
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