IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54378-9.html
   My bibliography  Save this article

Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen

Author

Listed:
  • Gavuthami Murugesan

    (92 Park Drive)

  • Rachel L. Paterson

    (92 Park Drive)

  • Rakesh Kulkarni

    (92 Park Drive)

  • Veronica Ilkow

    (92 Park Drive)

  • Richard J. Suckling

    (92 Park Drive)

  • Mary M. Connolly

    (92 Park Drive)

  • Vijaykumar Karuppiah

    (92 Park Drive)

  • Robert Pengelly

    (92 Park Drive)

  • Archana Jadhav

    (92 Park Drive)

  • Jose Donoso

    (92 Park Drive)

  • Tiaan Heunis

    (92 Park Drive)

  • Wilawan Bunjobpol

    (92 Park Drive)

  • Gwilym Philips

    (92 Park Drive)

  • Kafayat Ololade

    (92 Park Drive)

  • Daniel Kay

    (92 Park Drive)

  • Anshuk Sarkar

    (92 Park Drive)

  • Claire Barber

    (92 Park Drive)

  • Ritu Raj

    (92 Park Drive)

  • Carole Perot

    (92 Park Drive)

  • Tressan Grant

    (92 Park Drive)

  • Agatha Treveil

    (92 Park Drive)

  • Andrew Walker

    (92 Park Drive)

  • Marcin Dembek

    (92 Park Drive)

  • Dawn Gibbs-Howe

    (92 Park Drive)

  • Miriam Hock

    (92 Park Drive)

  • Ricardo J. Carreira

    (92 Park Drive)

  • Kate E. Atkin

    (92 Park Drive)

  • Lucy Dorrell

    (92 Park Drive)

  • Andrew Knox

    (92 Park Drive)

  • Sarah Leonard

    (92 Park Drive)

  • Mariolina Salio

    (92 Park Drive)

  • Luis F. Godinho

    (92 Park Drive)

Abstract

The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.

Suggested Citation

  • Gavuthami Murugesan & Rachel L. Paterson & Rakesh Kulkarni & Veronica Ilkow & Richard J. Suckling & Mary M. Connolly & Vijaykumar Karuppiah & Robert Pengelly & Archana Jadhav & Jose Donoso & Tiaan Heu, 2024. "Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54378-9
    DOI: 10.1038/s41467-024-54378-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54378-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54378-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Lucy C. Walters & Karl Harlos & Simon Brackenridge & Daniel Rozbesky & Jordan R. Barrett & Vitul Jain & Thomas S. Walter & Chris A. O’Callaghan & Persephone Borrow & Mireille Toebes & Scott G. Hansen , 2018. "Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Andrew Gibson & Ramesh Ram & Rama Gangula & Yueran Li & Eric Mukherjee & Amy M. Palubinsky & Chelsea N. Campbell & Michael Thorne & Katherine C. Konvinse & Phuti Choshi & Pooja Deshpande & Sarah Pedre, 2024. "Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Brooke D. Huisman & Ning Guan & Timo Rückert & Lee Garner & Nishant K. Singh & Andrew J. McMichael & Geraldine M. Gillespie & Chiara Romagnani & Michael E. Birnbaum, 2023. "High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54378-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.