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*
Department of Molecular Cell Biology, Vr
e Universiteit Medical Center, Amsterdam, The Netherlands; Departments of
Cell Biology and
Tumor Immunology, University Medical Center, Nijmegen, The Netherlands;
Department of Dermatology, University of Geneva, Geneva, Switzerland; and
¶ Institute for Research in Biomedicine, Bellinzona, Switzerland
Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.
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S. Ebner, Z. Ehammer, S. Holzmann, P. Schwingshackl, M. Forstner, P. Stoitzner, G. M. Huemer, P. Fritsch, and N. Romani Expression of C-type lectin receptors by subsets of dendritic cells in human skin Int. Immunol., June 1, 2004; 16(6): 877 - 887. [Abstract] [Full Text] [PDF]
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A. M. Woltman, N. Schlagwein, S. W. van der Kooij, and C. van Kooten The Novel Cyclophilin-Binding Drug Sanglifehrin A Specifically Affects Antigen Uptake Receptor Expression and Endocytic Capacity of Human Dendritic Cells J. Immunol., May 15, 2004; 172(10): 6482 - 6489. [Abstract] [Full Text] [PDF]
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G. Castellano, A. M. Woltman, A. J. Nauta, A. Roos, L. A. Trouw, M. A. Seelen, F. P. Schena, M. R. Daha, and C. van Kooten Maturation of dendritic cells abrogates C1q production in vivo and in vitro Blood, May 15, 2004; 103(10): 3813 - 3820. [Abstract] [Full Text] [PDF]
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A. Engering, S. J. van Vliet, K. Hebeda, D. G. Jackson, R. Prevo, S. K. Singh, T. B. H. Geijtenbeek, H. van Krieken, and Y. van Kooyk Dynamic Populations of Dendritic Cell-Specific ICAM-3 Grabbing Nonintegrin-Positive Immature Dendritic Cells and Liver/Lymph Node-Specific ICAM-3 Grabbing Nonintegrin-Positive Endothelial Cells in the Outer Zones of the Paracortex of Human Lymph Nodes Am. J. Pathol., May 1, 2004; 164(5): 1587 - 1595. [Abstract] [Full Text] [PDF]
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W. Liu, L. Tang, G. Zhang, H. Wei, Y. Cui, L. Guo, Z. Gou, X. Chen, D. Jiang, Y. Zhu, et al. Characterization of a Novel C-type Lectin-like Gene, LSECtin: DEMONSTRATION OF CARBOHYDRATE BINDING AND EXPRESSION IN SINUSOIDAL ENDOTHELIAL CELLS OF LIVER AND LYMPH NODE J. Biol. Chem., April 30, 2004; 279(18): 18748 - 18758. [Abstract] [Full Text] [PDF]
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A. Moris, C. Nobile, F. Buseyne, F. Porrot, J.-P. Abastado, and O. Schwartz DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation Blood, April 1, 2004; 103(7): 2648 - 2654. [Abstract] [Full Text] [PDF]
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 L.-Z. He, V. Ramakrishna, J. E. Connolly, X.-T. Wang, P. A. Smith, C. L. Jones, M. Valkova-Valchanova, A. Arunakumari, J. F. Treml, J. Goldstein, et al. A Novel Human Cancer Vaccine Elicits Cellular Responses to the Tumor-Associated Antigen, Human Chorionic Gonadotropin {beta} Clin. Cancer Res., March 15, 2004; 10(6): 1920 - 1927. [Abstract] [Full Text] [PDF]
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S. G. Turville, J. J. Santos, I. Frank, P. U. Cameron, J. Wilkinson, M. Miranda-Saksena, J. Dable, H. Stossel, N. Romani, M. Piatak Jr, et al. Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells Blood, March 15, 2004; 103(6): 2170 - 2179. [Abstract] [Full Text] [PDF]
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V. Ramakrishna, J. F. Treml, L. Vitale, J. E. Connolly, T. O'Neill, P. A. Smith, C. L. Jones, L.-Z. He, J. Goldstein, P. K. Wallace, et al. Mannose Receptor Targeting of Tumor Antigen pmel17 to Human Dendritic Cells Directs Anti-Melanoma T Cell Responses via Multiple HLA Molecules J. Immunol., March 1, 2004; 172(5): 2845 - 2852. [Abstract] [Full Text] [PDF]
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Y.-S. Kang, J. Y. Kim, S. A. Bruening, M. Pack, A. Charalambous, A. Pritsker, T. M. Moran, J. M. Loeffler, R. M. Steinman, and C. G. Park The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide of Streptococcus pneumoniae in the marginal zone of mouse spleen PNAS, January 6, 2004; 101(1): 215 - 220. [Abstract] [Full Text] [PDF]
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J. P. Hart, M. D. Gunn, and S. V. Pizzo A CD91-Positive Subset of CD11c+ Blood Dendritic Cells: Characterization of the APC that Functions to Enhance Adaptive Immune Responses against CD91-Targeted Antigens J. Immunol., January 1, 2004; 172(1): 70 - 78. [Abstract] [Full Text] [PDF]
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W. B. Klimstra, E. M. Nangle, M. S. Smith, A. D. Yurochko, and K. D. Ryman DC-SIGN and L-SIGN Can Act as Attachment Receptors for Alphaviruses and Distinguish between Mosquito Cell- and Mammalian Cell-Derived Viruses J. Virol., November 15, 2003; 77(22): 12022 - 12032. [Abstract] [Full Text] [PDF]
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L. Fontana, M. Nuzzo, L. Urbanelli, and P. Monaci General Strategy for Broadening Adenovirus Tropism J. Virol., October 15, 2003; 77(20): 11094 - 11104. [Abstract] [Full Text] [PDF]
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N. Frison, M. E. Taylor, E. Soilleux, M.-T. Bousser, R. Mayer, M. Monsigny, K. Drickamer, and A.-C. Roche Oligolysine-based Oligosaccharide Clusters: SELECTIVE RECOGNITION AND ENDOCYTOSIS BY THE MANNOSE RECEPTOR AND DENDRITIC CELL-SPECIFIC INTERCELLULAR ADHESION MOLECULE 3 (ICAM-3)-GRABBING NONINTEGRIN J. Biol. Chem., June 20, 2003; 278(26): 23922 - 23929. [Abstract] [Full Text] [PDF]
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I. van Die, S. J. van Vliet, A. K. Nyame, R. D. Cummings, C. M.C. Bank, B. Appelmelk, T. B.H. Geijtenbeek, and Y. van Kooyk The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x Glycobiology, June 1, 2003; 13(6): 471 - 478. [Abstract] [Full Text] [PDF]
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 D. McDonald, L. Wu, S. M. Bohks, V. N. KewalRamani, D. Unutmaz, and T. J. Hope Recruitment of HIV and Its Receptors to Dendritic Cell-T Cell Junctions Science, May 23, 2003; 300(5623): 1295 - 1297. [Abstract] [Full Text] [PDF]
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L. Martinez-Pomares, D. M. Reid, G. D. Brown, P. R. Taylor, R. J. Stillion, S. A. Linehan, S. Zamze, S. Gordon, and S. Y. C. Wong Analysis of mannose receptor regulation by IL-4, IL-10, and proteolytic processing using novel monoclonal antibodies J. Leukoc. Biol., May 1, 2003; 73(5): 604 - 613. [Abstract] [Full Text] [PDF]
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N. S. Stambach and M. E. Taylor Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells Glycobiology, May 1, 2003; 13(5): 401 - 410. [Abstract] [Full Text] [PDF]
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J. P. Gardner, R. J. Durso, R. R. Arrigale, G. P. Donovan, P. J. Maddon, T. Dragic, and W. C. Olson L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus PNAS, April 15, 2003; 100(8): 4498 - 4503. [Abstract] [Full Text] [PDF]
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S. Pohlmann, J. Zhang, F. Baribaud, Z. Chen, G. J. Leslie, G. Lin, A. Granelli-Piperno, R. W. Doms, C. M. Rice, and J. A. McKeating Hepatitis C Virus Glycoproteins Interact with DC-SIGN and DC-SIGNR J. Virol., April 1, 2003; 77(7): 4070 - 4080. [Abstract] [Full Text] [PDF]
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B. J. Appelmelk, I. van Die, S. J. van Vliet, C. M. J. E. Vandenbroucke-Grauls, T. B. H. Geijtenbeek, and Y. van Kooyk Cutting Edge: Carbohydrate Profiling Identifies New Pathogens That Interact with Dendritic Cell-Specific ICAM-3-Grabbing Nonintegrin on Dendritic Cells J. Immunol., February 15, 2003; 170(4): 1635 - 1639. [Abstract] [Full Text] [PDF]
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Y.-S. Kang, S. Yamazaki, T. Iyoda, M. Pack, S. A. Bruening, J. Y. Kim, K. Takahara, K. Inaba, R. M. Steinman, and C. G. Park SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran Int. Immunol., February 1, 2003; 15(2): 177 - 186. [Abstract] [Full Text] [PDF]
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C. Trumpfheller, C. G. Park, J. Finke, R. M. Steinman, and A. Granelli-Piperno Cell type-dependent retention and transmission of HIV-1 by DC-SIGN Int. Immunol., February 1, 2003; 15(2): 289 - 298. [Abstract] [Full Text] [PDF]
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S. H.E. Kaufmann and U. E. Schaible A Dangerous Liaison between Two Major Killers: Mycobacterium tuberculosis and HIV Target Dendritic Cells through DC-SIGN J. Exp. Med., January 6, 2003; 197(1): 1 - 5. [Full Text] [PDF]
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T. B.H. Geijtenbeek, S. J. van Vliet, E. A. Koppel, M. Sanchez-Hernandez, C. M.J.E. Vandenbroucke-Grauls, B. Appelmelk, and Y. van Kooyk Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function J. Exp. Med., January 6, 2003; 197(1): 7 - 17. [Abstract] [Full Text] [PDF]
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G. Lin, G. Simmons, S. Pohlmann, F. Baribaud, H. Ni, G. J. Leslie, B. S. Haggarty, P. Bates, D. Weissman, J. A. Hoxie, et al. Differential N-Linked Glycosylation of Human Immunodeficiency Virus and Ebola Virus Envelope Glycoproteins Modulates Interactions with DC-SIGN and DC-SIGNR J. Virol., December 20, 2002; 77(2): 1337 - 1346. [Abstract] [Full Text] [PDF]
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L. Bonifaz, D. Bonnyay, K. Mahnke, M. Rivera, M. C. Nussenzweig, and R. M. Steinman Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance J. Exp. Med., December 16, 2002; 196(12): 1627 - 1638. [Abstract] [Full Text] [PDF]
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K. W. Schjetne, K. M. Thompson, T. Aarvak, B. Fleckenstein, L. M. Sollid, and B. Bogen A mouse C{kappa}-specific T cell clone indicates that DC-SIGN is an efficient target for antibody-mediated delivery of T cell epitopes for MHC class II presentation Int. Immunol., December 1, 2002; 14(12): 1423 - 1430. [Abstract] [Full Text] [PDF]
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E. J. Ryan, A. J. Marshall, D. Magaletti, H. Floyd, K. E. Draves, N. E. Olson, and E. A. Clark Dendritic Cell-Associated Lectin-1: A Novel Dendritic Cell-Associated, C-Type Lectin-Like Molecule Enhances T Cell Secretion of IL-4 J. Immunol., November 15, 2002; 169(10): 5638 - 5648. [Abstract] [Full Text] [PDF]
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W. M. Krupa, M. Dewan, M.-S. Jeon, P. J. Kurtin, B. R. Younge, J. J. Goronzy, and C. M. Weyand Trapping of Misdirected Dendritic Cells in the Granulomatous Lesions of Giant Cell Arteritis Am. J. Pathol., November 1, 2002; 161(5): 1815 - 1823. [Abstract] [Full Text] [PDF]
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M. T. Yu Kimata, M. Cella, J. E. Biggins, C. Rorex, R. White, S. Hicks, J. M. Wilson, P. G. Patel, J. S. Allan, M. Colonna, et al. Capture and Transfer of Simian Immunodeficiency Virus by Macaque Dendritic Cells Is Enhanced by DC-SIGN J. Virol., October 25, 2002; 76(23): 11827 - 11836. [Abstract] [Full Text] [PDF]
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M. J. Raftery, A. A. Kraus, R. Ulrich, D. H. Kruger, and G. Schonrich Hantavirus Infection of Dendritic Cells J. Virol., October 2, 2002; 76(21): 10724 - 10733. [Abstract] [Full Text] [PDF]
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