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

doi:10.1083/jcb.151.3.673

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 Mahnke^a, Ming Guo^b, Sena Lee^b, Homero Sepulveda^c, Suzy L. Swain^c, Michel Nussenzweig^b, and Ralph M. Steinman^a

^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 cellsthrough early endosomes. We now find in dendritic cells thatthe DEC-205 multilectin receptor targets late endosomes or lysosomesrich in major histocompatibility complex class II (MHC II) products,whereas the homologous macrophage mannose receptor (MMR), asexpected, is found in more peripheral endosomes. To analyzethis finding, the cytosolic tails of DEC-205 and MMR were fusedto the external domain of the CD16 Fc ${gamma}$ receptor and studied instable L cell transfectants. The two cytosolic domains eachmediated rapid uptake of human immunoglobulin (Ig)G followedby recycling of intact CD16 to the cell surface. However, theDEC-205 tail recycled the CD16 through MHC II–positivelate endosomal/lysosomal vacuoles and also mediated a 100-foldincrease in antigen presentation. The mechanism of late endosomaltargeting, which occurred in the absence of human IgG, involvedtwo functional regions: a membrane-proximal region with a coatedpit sequence for uptake, and a distal region with an EDE triadfor the unusual deeper targeting. Therefore, the DEC-205 cytosolicdomain mediates a new pathway of receptor-mediated endocytosisthat entails efficient recycling through late endosomes anda greatly enhanced efficiency of antigen presentation to CD4⁺T cells.

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

Abbreviations used in this paper: aggHuIgG, aggregated humanIgG; BCR, B cell antigen receptor; CHX, cycloheximide; DC, dendriticcell; ICAM, intracellular adhesion molecule; LAMP-1, lysosome-associatedmembrane protein 1; LDLR, low-density lipoprotein receptor;MMR, macrophage mannose receptor; MHC II, major histocompatibilitycomplex class II; MIIC, MHC II compartment; PLA2R, phospholipaseA2 receptor; TfR, transferrin receptor.

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