IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52772-x.html
   My bibliography  Save this article

Tapasin assembly surveillance by the RNF185/Membralin ubiquitin ligase complex regulates MHC-I surface expression

Author

Listed:
  • Michael L. Weijer

    (University of Oxford)

  • Krishna Samanta

    (University of Oxford)

  • Nikita Sergejevs

    (University of Oxford)

  • LuLin Jiang

    (Sanford Burnham Prebys Medical Discovery Institute
    Altos Labs-Bay Institute of Science)

  • Maria Emilia Dueñas

    (Newcastle University
    Telethon Kids Institute, Perth)

  • Tiaan Heunis

    (University of Oxford
    Immunocore Ltd)

  • Timothy Y. Huang

    (Sanford Burnham Prebys Medical Discovery Institute)

  • Randal J. Kaufman

    (Sanford Burnham Prebys Medical Discovery Institute)

  • Matthias Trost

    (Newcastle University)

  • Sumana Sanyal

    (University of Oxford)

  • Sally A. Cowley

    (University of Oxford
    University of Oxford)

  • Pedro Carvalho

    (University of Oxford)

Abstract

Immune surveillance by cytotoxic T cells eliminates tumor cells and cells infected by intracellular pathogens. This process relies on the presentation of antigenic peptides by Major Histocompatibility Complex class I (MHC-I) at the cell surface. The loading of these peptides onto MHC-I depends on the peptide loading complex (PLC) at the endoplasmic reticulum (ER). Here, we uncovered that MHC-I antigen presentation is regulated by ER-associated degradation (ERAD), a protein quality control process essential to clear misfolded and unassembled proteins. An unbiased proteomics screen identified the PLC component Tapasin, essential for peptide loading onto MHC-I, as a substrate of the RNF185/Membralin ERAD complex. Loss of RNF185/Membralin resulted in elevated Tapasin steady state levels and increased MHC-I at the surface of professional antigen presenting cells. We further show that RNF185/Membralin ERAD complex recognizes unassembled Tapasin and limits its incorporation into PLC. These findings establish a novel mechanism controlling antigen presentation and suggest RNF185/Membralin as a potential therapeutic target to modulate immune surveillance.

Suggested Citation

  • Michael L. Weijer & Krishna Samanta & Nikita Sergejevs & LuLin Jiang & Maria Emilia Dueñas & Tiaan Heunis & Timothy Y. Huang & Randal J. Kaufman & Matthias Trost & Sumana Sanyal & Sally A. Cowley & Pe, 2024. "Tapasin assembly surveillance by the RNF185/Membralin ubiquitin ligase complex regulates MHC-I surface expression," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52772-x
    DOI: 10.1038/s41467-024-52772-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52772-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52772-x?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. John B. Grigg & Arthi Shanmugavadivu & Tommy Regen & Christopher N. Parkhurst & Anees Ahmed & Ann M. Joseph & Michael Mazzucco & Konrad Gronke & Andreas Diefenbach & Gerard Eberl & Timothy Vartanian &, 2021. "Antigen-presenting innate lymphoid cells orchestrate neuroinflammation," Nature, Nature, vol. 600(7890), pages 707-712, December.
    2. Jiansheng Jiang & Daniel K. Taylor & Ellen J. Kim & Lisa F. Boyd & Javeed Ahmad & Michael G. Mage & Hau V. Truong & Claire H. Woodward & Nikolaos G. Sgourakis & Peter Cresswell & David H. Margulies & , 2022. "Structural mechanism of tapasin-mediated MHC-I peptide loading in antigen presentation," Nature Communications, Nature, vol. 13(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 C. McShan & David Flores-Solis & Yi Sun & Samuel E. Garfinkle & Jugmohit S. Toor & Michael C. Young & Nikolaos G. Sgourakis, 2023. "Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition," Nature Communications, Nature, vol. 14(1), pages 1-19, 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_s41467-024-52772-x. 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.