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

Tejas Menon, Patricia T. Illing, Priyanka Chaurasia, Hayley A. McQuilten, Chloe Shepherd, Louise C. Rowntree, Jan Petersen, Dene R. Littler, Grace Khuu, Ziyi Huang, Lilith F. Allen, Steve Rockman, Jane Crowe, Katie L. Flanagan, Linda M. Wakim, Thi H. O. Nguyen, Nicole A. Mifsud, Jamie Rossjohn, Anthony W. Purcell, Carolien E. Sandt and Katherine Kedzierska ()
Additional contact information
Tejas Menon: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Patricia T. Illing: Monash University
Priyanka Chaurasia: Monash University
Hayley A. McQuilten: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Chloe Shepherd: Monash University
Louise C. Rowntree: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Jan Petersen: Monash University
Dene R. Littler: Monash University
Grace Khuu: Monash University
Ziyi Huang: Monash University
Lilith F. Allen: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Steve Rockman: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Jane Crowe: Deepdene Surgery
Katie L. Flanagan: Launceston General Hospital
Linda M. Wakim: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Thi H. O. Nguyen: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Nicole A. Mifsud: Monash University
Jamie Rossjohn: Monash University
Anthony W. Purcell: Monash University
Carolien E. Sandt: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
Katherine Kedzierska: University of Melbourne, at the Peter Doherty Institute for Infection and Immunity

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47576-y

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