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

Menon, Tejas, Illing, Patricia T., Chaurasia, Priyanka, McQuilten, Hayley A., Shepherd, Chloe, Rowntree, Louise C., Petersen, Jan, Littler, Dene R., Khuu, Grace, Huang, Ziyi, Allen, Lilith F., Rockman, Steve, Crowe, Jane, Flanagan, Katie L., Wakim, Linda M., Nguyen, Thi H. O., Mifsud, Nicole A., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Purcell, Anthony W., van de Sandt, Carolien E. and Kedzierska, Katherine 2024. CD8 + T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age. Nature Communications 15 , 3387. 10.1038/s41467-024-47576-y

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Abstract

Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ 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+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer+CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02-restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	30 April 2024
Date of Acceptance:	3 April 2024
Last Modified:	30 Apr 2024 09:15
URI:	https://orca.cardiff.ac.uk/id/eprint/168500

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