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Published online 30 October 2000. doi:10.1083/jcb.151.3.673
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© The Rockefeller University Press, 0021-9525/2000//673 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 673-684

Original Article

The Dendritic Cell Receptor for Endocytosis, Dec-205, Can Recycle and Enhance Antigen Presentation via Major Histocompatibility Complex Class II–Positive Lysosomal Compartments



Karsten Mahnkea, Ming Guob, Sena Leeb, Homero Sepulvedac, Suzy L. Swainc, Michel Nussenzweigb, and Ralph M. Steinmana

a Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York, 10021
b Howard Hughes Medical Institute, The Rockefeller University, New York, New York, 10021
c The Trudeau Institute, Saranac Lake, New York 12983
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY, 10021-6399.(212) 327-8875(212) 327-8106

Many receptors for endocytosis recycle into and out of cells through early endosomes. We now find in dendritic cells that the DEC-205 multilectin receptor targets late endosomes or lysosomes rich in major histocompatibility complex class II (MHC II) products, whereas the homologous macrophage mannose receptor (MMR), as expected, is found in more peripheral endosomes. To analyze this finding, the cytosolic tails of DEC-205 and MMR were fused to the external domain of the CD16 Fc{gamma} receptor and studied in stable L cell transfectants. The two cytosolic domains each mediated rapid uptake of human immunoglobulin (Ig)G followed by recycling of intact CD16 to the cell surface. However, the DEC-205 tail recycled the CD16 through MHC II–positive late endosomal/lysosomal vacuoles and also mediated a 100-fold increase in antigen presentation. The mechanism of late endosomal targeting, which occurred in the absence of human IgG, involved two functional regions: a membrane-proximal region with a coated pit sequence for uptake, and a distal region with an EDE triad for the unusual deeper targeting. Therefore, the DEC-205 cytosolic domain mediates a new pathway of receptor-mediated endocytosis that entails efficient recycling through late endosomes and a greatly enhanced efficiency of antigen presentation to CD4+ T cells.

Key Words: dendritic cell • antigen presentation • DEC-205 • MHC class II • endocytosis

© 2000 The Rockefeller University Press

Abbreviations used in this paper: aggHuIgG, aggregated human IgG; BCR, B cell antigen receptor; CHX, cycloheximide; DC, dendritic cell; ICAM, intracellular adhesion molecule; LAMP-1, lysosome-associated membrane protein 1; LDLR, low-density lipoprotein receptor; MMR, macrophage mannose receptor; MHC II, major histocompatibility complex class II; MIIC, MHC II compartment; PLA2R, phospholipase A2 receptor; TfR, transferrin receptor.


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