The Adaptor Protein AP-3 Is Required for CD1d-Mediated Antigen Presentation of Glycosphingolipids and Development of Vα14i NKT Cells

Dirk Elewaut, Anna P. Lawton, Niranjana A. Nagarajan, Emanual Michael Maverakis, Archana Khurana, Stefan Höning, Chris A. Benedict, Eli Sercarz, Oddmund Bakke, Mitchell Kronenberg, Theodore I. Prigozy

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Relatively little is known about the pathway leading to the presentation of glycolipids by CD1 molecules. Here we show that the adaptor protein complex 3 (AP-3) is required for the efficient presentation of glycolipid antigens that require internalization and processing. AP-3 interacts with mouse CD1d, and cells from mice deficient for AP-3 have increased cell surface levels of CD1d and decreased expression in late endosomes. Spleen cells from AP-3-deficient mice have a reduced ability to present glycolipids to natural killer T (NKT) cells. Furthermore, AP-3-deficient mice have a significantly reduced NKT cell population, although this is not caused by self-tolerance that might result from increased CD1d surface levels. These data suggest that the generation of the endogenous ligand that selects NKT cells may also be AP-3 dependent. However, the function of MHC class II-reactive CD4+ T lymphocytes is not altered by AP-3 deficiency. Consistent with this divergence from the class II pathway, NKT cell development and antigen presentation by CD1d are not reduced by invariant chain deficiency. These data demonstrate that the AP-3 requirement is a particular attribute of the CD1d pathway in mice and that, although MHC class II molecules and CD1d are both found in late endosomes or lysosomes, different pathways mediate their intracellular trafficking.

Original languageEnglish (US)
Pages (from-to)1133-1146
Number of pages14
JournalJournal of Experimental Medicine
Volume198
Issue number8
DOIs
StatePublished - Oct 20 2003

Keywords

  • Intracellular localization
  • Lipid antigen
  • Lymphocyte selection
  • MHC II trafficking pathway
  • Trafficking

ASJC Scopus subject areas

  • Immunology

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    Elewaut, D., Lawton, A. P., Nagarajan, N. A., Maverakis, E. M., Khurana, A., Höning, S., Benedict, C. A., Sercarz, E., Bakke, O., Kronenberg, M., & Prigozy, T. I. (2003). The Adaptor Protein AP-3 Is Required for CD1d-Mediated Antigen Presentation of Glycosphingolipids and Development of Vα14i NKT Cells. Journal of Experimental Medicine, 198(8), 1133-1146. https://doi.org/10.1084/jem.20030143