HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 33, 34818-34826, August 13, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/33/34818    most recent M404608200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Karacsonyi, C. Articles by Lindner, R. Search for Related Content PubMed PubMed Citation Articles by Karacsonyi, C. Articles by Lindner, R. Social Bookmarking                      What's this?

Association of Major Histocompatibility Complex II with Cholesterol- and Sphingolipid-rich Membranes Precedes Peptide Loading^*

Claudia Karacsonyi, Ruth Knorr, Angela Fülbier, and Robert Lindner

From the Department of Cell Biology in the Center of Anatomy, Hannover Medical School, 30625 Hannover, Germany

Major histocompatibility complex class II protein (MHC II) molecules present antigenic peptides to CD4-positive T-cells. Efficient T cell stimulation requires association of MHC II with membrane microdomains organized by cholesterol and glycosphingolipids or by tetraspanins. Using detergent extraction at 37 °C combined with a modified flotation assay, we investigated the sequence of events leading to the association of MHC II with cholesterol- and glycosphingolipid-rich membranes (DRMs) that are distinct from tetraspanins. We find two stages of association of MHC II with DRMs. In stage one, complexes of MHC II and invariant chain, a chaperone involved in MHC II transport, enter DRMs in the Golgi stack. In early endosomes, these complexes are almost quantitatively associated with DRMs. Upon transport to late endocytic compartments, MHC II-bound invariant chain is stepwise proteolyzed to the MHC class II-associated invariant chain peptide (CLIP) that remains MHC II-bound and retains a preference for DRMs. At the transition between the two stages, CLIP is exchanged against processed antigens, and the resulting MHC II-peptide complexes are transported to the cell surface. In the second stage, MHC II shows a lower overall association with DRMs. However, surface MHC II molecules occupied with peptides that induce resistance to denaturation by SDS are enriched in DRMs relative to SDS-sensitive MHC II-peptide complexes. Likewise, MHC II molecules loaded with long-lived processing products of hen-egg lysozyme containing the immunodominant epitope 48–61 show a very high preference for DRMs. Thus after an initial mainly intracellular stage of high DRM association, MHC II moves to a second stage in which its preference for DRMs is modulated by bound peptides.

Received for publication, April 26, 2004 , and in revised form, June 2, 2004.

^* This work was supported by the HiLF program of the Hannover Medical School (to R. L.) and by German Research Foundation Grant SFB 621 (to R. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Tel.: 49-511-532-2918; Fax: 49-511-532-3903; E-mail: rli{at}zellbiologie.mh-hannover.de.

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

This article has been cited by other articles:

				R. Knorr, C. Karacsonyi, and R. Lindner Endocytosis of MHC molecules by distinct membrane rafts J. Cell Sci., May 15, 2009; 122(10): 1584 - 1594. [Abstract] [Full Text] [PDF]

				C. Gelin, I. Sloma, D. Charron, and N. Mooney Regulation of MHC II and CD1 antigen presentation: from ubiquity to security J. Leukoc. Biol., February 1, 2009; 85(2): 215 - 224. [Abstract] [Full Text] [PDF]

				I. Sloma, M.-T. Zilber, T. Vasselon, N. Setterblad, M. Cavallari, L. Mori, G. De Libero, D. Charron, N. Mooney, and C. Gelin Regulation of CD1a Surface Expression and Antigen Presentation by Invariant Chain and Lipid Rafts J. Immunol., January 15, 2008; 180(2): 980 - 987. [Abstract] [Full Text] [PDF]

				H. Imhoff, V. von Messling, G. Herrler, and L. Haas Canine Distemper Virus Infection Requires Cholesterol in the Viral Envelope J. Virol., April 15, 2007; 81(8): 4158 - 4165. [Abstract] [Full Text] [PDF]

				A.K.M. Mahbub Hasan, Z. Ou, K. Sakakibara, S. Hirahara, T. Iwasaki, K.-i. Sato, and Y. Fukami Characterization of Xenopus egg membrane microdomains containing uroplakin Ib/III complex: roles of their molecular interactions for subcellular localization and signal transduction. Genes Cells, February 1, 2007; 12(2): 251 - 267. [Abstract] [Full Text] [PDF]

				C. Karacsonyi, T. Bedke, N. Hinrichsen, R. Schwinzer, and R. Lindner MHC II molecules and invariant chain reside in membranes distinct from conventional lipid rafts J. Leukoc. Biol., November 1, 2005; 78(5): 1097 - 1105. [Abstract] [Full Text] [PDF]