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

Author

Listed:
  • 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
    CSL Seqirus Ltd)

  • Jane Crowe

    (Deepdene Surgery)

  • Katie L. Flanagan

    (Launceston General Hospital
    University of Tasmania
    RMIT University)

  • 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
    Cardiff University School of Medicine)

  • Anthony W. Purcell

    (Monash University)

  • Carolien E. Sandt

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity
    Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam)

  • Katherine Kedzierska

    (University of Melbourne, at the Peter Doherty Institute for Infection and Immunity)

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.

Suggested Citation

  • 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 R, 2024. "CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47576-y
    DOI: 10.1038/s41467-024-47576-y
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    References listed on IDEAS

    as
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