The Journal of Experimental Medicine
PBL InterferonSource
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 13 October 2003 doi:10.1084/jem.20030143
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Elewaut, D.
Right arrow Articles by Prigozy, T. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Elewaut, D.
Right arrow Articles by Prigozy, T. I.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/10/1133 $5.00
The Journal of Experimental Medicine, Volume 198, Number 8, 1133-1146

The Adaptor Protein AP-3 Is Required for CD1d-Mediated Antigen Presentation of Glycosphingolipids and Development of V{alpha}14i NKT Cells

Dirk Elewaut1, Anna P. Lawton1, Niranjana A. Nagarajan1,2, Emanual Maverakis1, Archana Khurana1, Stefan Höning3, Chris A. Benedict1, Eli Sercarz1, Oddmund Bakke4, Mitchell Kronenberg1,2 and Theodore I. Prigozy1

1 La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
2 Division of Biology, University of California San Diego, La Jolla, CA 92093
3 Biochemistry II, University of Göttingen, Göttingen 37073, Germany
4 Center for Vaccinology and Immunotherapy, Department of Biology, University of Oslo, Oslo NO-0316, Norway

Address correspondence to Mitchell Kronenberg, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: (858) 678-4540; Fax: (858) 678-4595; email: mitch{at}liai.org

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.

Key Words: intracellular localization • trafficking • lipid antigen • lymphocyte selection • MHC II trafficking pathway


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS