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Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86

Author

Listed:
  • Haiyin Liu

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Kayla R. Wilson

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Ashley M. Firth

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Christophe Macri

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Patrick Schriek

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Annabelle B. Blum

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Javiera Villar

    (PSL Research University, INSERM, U932)

  • Samuel Wormald

    (The Walter and Eliza Hall Institute of Medical Research)

  • Mitch Shambrook

    (La Trobe University)

  • Bangyan Xu

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

  • Hui Jing Lim

    (The University of Melbourne)

  • Hamish E. G. McWilliam

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute
    The University of Melbourne)

  • Andrew F. Hill

    (La Trobe University)

  • Laura E. Edgington-Mitchell

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute
    New York University College of Dentistry
    Monash University)

  • Irina Caminschi

    (Monash University)

  • Mireille H. Lahoud

    (Monash University)

  • Elodie Segura

    (PSL Research University, INSERM, U932)

  • Marco J. Herold

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Jose A. Villadangos

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute
    The University of Melbourne)

  • Justine D. Mintern

    (The University of Melbourne, Bio21 Molecular Science and Biotechnology Institute)

Abstract

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses.

Suggested Citation

  • Haiyin Liu & Kayla R. Wilson & Ashley M. Firth & Christophe Macri & Patrick Schriek & Annabelle B. Blum & Javiera Villar & Samuel Wormald & Mitch Shambrook & Bangyan Xu & Hui Jing Lim & Hamish E. G. M, 2022. "Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29524-w
    DOI: 10.1038/s41467-022-29524-w
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    References listed on IDEAS

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    1. Jeoung-Sook Shin & Melanie Ebersold & Marc Pypaert & Lelia Delamarre & Adam Hartley & Ira Mellman, 2006. "Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination," Nature, Nature, vol. 444(7115), pages 115-118, November.
    2. Xiaolong Lu & Konstantin R. Malley & Caitlin C. Brenner & Olga Koroleva & Sergey Korolev & Brian P. Downes, 2016. "A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
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    Cited by:

    1. Lei Xia & Anastasia Komissarova & Arielle Jacover & Yehuda Shovman & Sebastian Arcila-Barrera & Sharona Tornovsky-Babeay & Milsee Mol Jaya Prakashan & Abdelmajeed Nasereddin & Inbar Plaschkes & Yuval , 2023. "Systematic identification of gene combinations to target in innate immune cells to enhance T cell activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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