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First published online 21 April 2009
doi: 10.1242/jcs.039727

Journal of Cell Science 122, 1584-1594 (2009)
Published by The Company of Biologists 2009
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Research Article

Endocytosis of MHC molecules by distinct membrane rafts

Ruth Knorr, Claudia Karacsonyi and Robert Lindner*

Department of Cell Biology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

* Author for correspondence (e-mail: lindner.robert{at}mh-hannover.de)

Accepted 3 February 2009

In B-lymphocytes, endocytosis of MHC I and MHC II molecules is important for the cross-priming and presentation of labile antigens, respectively. Here, we report that MHC I and MHC II were internalized by separate endocytic carriers that lacked transferrin receptor. Cholera toxin B was co-internalized with MHC II, but not with MHC I, suggesting that the CLIC/GEEC pathway is involved in the uptake of MHC II. Endocytosis of MHC I and MHC II was inhibited by filipin, but only MHC II showed a strong preference for a membrane raft environment in a co-clustering analysis with GM1. By using a novel method for the extraction of detergent-resistant membranes (DRMs), we observed that MHC I and MHC II associate with two distinct types of DRMs. These differ in density, protein content, lipid composition, and ultrastructure. The results of cell surface biotinylation and subsequent DRM isolation show that precursors for both DRMs coexist in the plasma membrane. Moreover, clustering of MHC proteins at the cell surface resulted in shifts of the respective DRMs, revealing proximity-induced changes in the membrane environment. Our results suggest that the preference of MHC I and MHC II for distinct membrane rafts directs them to different cellular entry points.

Key words: Endocytosis, CLIC/GEEC pathway, Major histocompatibility complex, Antigen presentation, Membrane rafts, Detergent-resistant membranes


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