CD1d function is regulated by microsomal triglyceride transfer protein

Suzana Brozovic, Takashi Nagaishi, Masaru Yoshida, Stephanie Betz, Azucena Salas, Daohong Chen, Arthur Kaser, Jonathan Glickman, Timothy Kuo, Alicia Little, Jamin Morrison, Nadia Corazza, Jin Yong Kim, Sean P. Colgan, Stephen G. Young, Mark Exley, Richard S. Blumberg

    Research output: Contribution to journalArticlepeer-review

    Abstract

    CD1d is a major histocompatibility complex (MHC) class I-related molecule that functions in glycolipid antigen presentation to distinct subsets of T cells that express natural killer receptors and an invariant T-cell receptor-α chain (invariant NKT cells). The acquisition of glycolipid antigens by CD1d occurs, in part, in endosomes through the function of resident lipid transfer proteins, namely saposins. Here we show that microsomal triglyceride transfer protein (MTP), a protein that resides in the endoplasmic reticulum of hepatocytes and intestinal epithelial cells (IECs) and is essential for lipidation of apolipoprotein B, associates with CD1d in hepatocytes. Hepatocytes from animals in which Mttp (the gene encoding MTP) has been conditionally deleted, and IECs in which Mttp gene products have been silenced, are unable to activate invariant NKT cells. Conditional deletion of the Mttp gene in hepatocytes is associated with a redistribution of CD1d expression, and Mttp-deleted mice are resistant to immunopathologies associated with invariant NKT cell-mediated hepatitis and colitis. These studies indicate that the CD1d-regulating function of MTP in the endoplasmic reticulum is complementary to that of the saposins in endosomes in vivo.
    Original languageEnglish
    Pages (from-to)535-539
    Number of pages4
    JournalNature Medicine
    Volume10
    Issue number5
    DOIs
    Publication statusPublished - May 2004

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