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International Immunology, Vol. 5, No. 8, pp. 903-917,August 1993
© 1993 Japanese Society for Immunology

Intracellular distribution of the MHC class II molecules and the associated invariant chain (li) in different cell lines

Anne Simonsen, Frank Momburg1, Johannes Drexler1, Günther J. Hämmerling1 and Oddmund Bakke

Department of Molecular Cell Biology, University of Oslo PO Box 1050, 0316 Oslo, Norway
1 Deutsches Krebsforschungszentrum PF 101949, 6900 Heidelberg 1, Germany

Correspondence to: Correspondence to: A. Simonsen

Intracellular localization and routing of MHC class II molecules and the associated invariant chain (II) were studied using rat-2 cells and HeLa cells stably transfected with the murine class II genes A{alpha}kAßk (Ak) alone or supertransfected with human II or a truncated {Delta}20II lacking the endosomal sorting signal within II. Weshow that II and {Delta}20II are able to bind the class II molecules and replace the highly homologous murine II in class II sorting. Expression of transfected II or {Delta}20II also result in more efficient transport of class II molecules from the ER. There are, however, cell type specific differences in the intracellular routing of the class II molecules. The endosomal sorting signal within II is required to target class II molecules to endosomes in HeLa cells, whereas class II molecules alone enter endosomes in rat-2 cells. Class II molecules cannot direct the associated {Delta}20II to endosomes, suggesting that they follow a direct route to the cell surface and the majority of class II may enter endosomes by internalization. This is also supported by the long lived presence of class II molecules in endosomes after arresting protein transport with cycloheximide or brefeldin A. Class II molecules expressed alone or together with II are located in the whole endosomal pathway in rat-2 cells. However, full length II is required to target the class II molecules to vesicles that are more chloroquine sensitive than vesicles containing class II molecules alone. Our results thus indicate that II is responsible for endosomal sorting of class II molecules in HeLa cells, whereas in rat-2 cells the presence of II leads to an altered endosomal distribution.

Keywords: intracellular sorting, chloroquine effect

Received 23 November 1992, accepted 30 April 1993.


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