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MBC in Press, published online ahead of print June 13, 2003
Mol. Biol. Cell 10.1091/mbc.E02-11-0744

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Submitted on November 18, 2002
Revised on February 26, 2003
Accepted on March 13, 2003

CD1 and MHC class II molecules follow a different course during dendritic cell maturation

N.N. van der Wel1, M. Sugita2, D.M. Broekhuis-Fluitsma3, X. Cao4, G. Schreibelt1, M.B. Brenner5, and P.J. Peters6*

1 The Netherlands Cancer Institute, Plesmanlaan 121 - H4, 1066 CX Amsterdam
2 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
3 Molecular Cell Biology, Free University Amsterdam
4 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
5 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
6 The Netherlands Cancer Institute, Plesmanlaan 121 - H4, 1066 CX Amsterdam, Molecular Cell Biology, Free University Amsterdam

* Corresponding author. E-mail address: p.peters{at}nki.nl.

The maturation of dendritic cells is accompanied by the redistribution of MHC class II molecules from the lysosomal MHC class II compartment (MIIC) to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Here we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to LPS-induced maturation. However the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separates peptide and lipid antigen presenting molecules during dendritic cell maturation.




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