IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v409y2001i6821d10.1038_35055582.html
   My bibliography  Save this article

Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation

Author

Listed:
  • Michael Demetriou

    (Samuel Lunenfeld Research Institute, Mount Sinai Hospital
    University of Toronto)

  • Maria Granovsky

    (Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • Sue Quaggin

    (Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • James W. Dennis

    (Samuel Lunenfeld Research Institute, Mount Sinai Hospital
    University of Toronto)

Abstract

T-cell activation requires clustering of a threshold number of T-cell receptors (TCRs) at the site of antigen presentation, a number that is reduced by CD28 co-receptor recruitment of signalling proteins to TCRs1,2,3,4,5. Here we demonstrate that a deficiency in β1,6 N-acetylglucosaminyltransferase V (Mgat5), an enzyme in the N-glycosylation pathway, lowers T-cell activation thresholds by directly enhancing TCR clustering. Mgat5-deficient mice showed kidney autoimmune disease, enhanced delayed-type hypersensitivity, and increased susceptibility to experimental autoimmune encephalomyelitis. Recruitment of TCRs to agonist-coated beads, TCR signalling, actin microfilament re-organization, and agonist-induced proliferation were all enhanced in Mgat5-/- T cells. Mgat5 initiates GlcNAc β1,6 branching on N-glycans, thereby increasing N-acetyllactosamine6, the ligand for galectins7,8, which are proteins known to modulate T-cell proliferation and apoptosis9,10. Indeed, galectin-3 was associated with the TCR complex at the cell surface, an interaction dependent on Mgat5. Pre-treatment of wild-type T cells with lactose to compete for galectin binding produced a phenocopy of Mgat5-/- TCR clustering. These data indicate that a galectin–glycoprotein lattice strengthened by Mgat5-modified glycans restricts TCR recruitment to the site of antigen presentation. Dysregulation of Mgat5 in humans may increase susceptibility to autoimmune diseases, such as multiple sclerosis.

Suggested Citation

  • Michael Demetriou & Maria Granovsky & Sue Quaggin & James W. Dennis, 2001. "Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation," Nature, Nature, vol. 409(6821), pages 733-739, February.
  • Handle: RePEc:nat:nature:v:409:y:2001:i:6821:d:10.1038_35055582
    DOI: 10.1038/35055582
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35055582
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/35055582?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guy Werlen & Mei-Ling Li & Luca Tottone & Victoria da Silva-Diz & Xiaoyang Su & Daniel Herranz & Estela Jacinto, 2022. "Dietary glucosamine overcomes the defects in αβ-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:nature:v:409:y:2001:i:6821:d:10.1038_35055582. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.