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Published 1 October 2001. doi:10.1083/jcb.200103071
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© The Rockefeller University Press, 0021-9525/2001/10/53 $5.00
The Journal of Cell Biology, Volume 155, Number 1, October 1, 2001 53-64

Article

 Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells

Monique Kleijmeer1, Georg Ramm1, Danita Schuurhuis2, Janice Griffith1, Maria Rescigno3, Paola Ricciardi-Castagnoli3, Alexander Y. Rudensky4, Ferry Ossendorp4, Cornelis J.M. Melief4, Willem Stoorvogel1 and Hans J. Geuze1

1 Department of Cell Biology, University Medical Center, Institute of Biomembranes and Center for Biomedical Genetics, 3584 CX Utrecht, Netherlands
2 Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, Netherlands
3 Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy
4 Howard Hughes Medical Institute, University of Washington, School of Medicine, Seattle, WA 98195

Address correspondence to Hans J. Geuze, Dept. of Cell Biology, UMC, Institute of Biomembranes, Heidelberglaan 100, Rm. G02.525, 3584 CX Utrecht, Netherlands. Tel.: 31-30-2507652. Fax: 31-30-2541797. E-mail: h.j.geuze{at}lab.azu.nl

Immature dendritic cells (DCs) sample their environment for antigens and after stimulation present peptide associated with major histocompatibility complex class II (MHC II) to naive T cells. We have studied the intracellular trafficking of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored intracellularly at the internal vesicles of multivesicular bodies (MVBs). In contrast, DM, an accessory molecule required for peptide loading, was located predominantly at the limiting membrane of MVBs. After stimulation, the internal vesicles carrying MHC II were transferred to the limiting membrane of the MVB, bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs transformed into long tubular organelles that extended into the periphery of the cells. Vesicles that were formed at the tips of these tubules nonselectively incorporated MHC II and DM and presumably mediated transport to the plasma membrane. We propose that in maturing DCs, the reorganization of MVBs is fundamental for the timing of MHC II antigen loading and transport to the plasma membrane.

Key Words: antigen presentation; dendritic cells; endosomes; lysosomes; major histocompatibility complex


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