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Science 7 December 2001:
Vol. 294. no. 5549, pp. 2163 - 2166
DOI: 10.1126/science.1066371
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Reports

Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR

Hadar Feinberg,1 Daniel A. Mitchell,2 Kurt Drickamer,2 William I. Weis1*

Dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.

1 Department of Structural Biology and Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
*   To whom correspondence should be addressed. E-mail: bill.weis{at}stanford.edu

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Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function.
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 (2003)
J. Exp. Med. 197, 7-17
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DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells.
L. Tailleux, O. Schwartz, J.-L. Herrmann, E. Pivert, M. Jackson, A. Amara, L. Legres, D. Dreher, L. P. Nicod, J. C. Gluckman, et al. (2003)
J. Exp. Med. 197, 121-127
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Differential N-Linked Glycosylation of Human Immunodeficiency Virus and Ebola Virus Envelope Glycoproteins Modulates Interactions with DC-SIGN and DC-SIGNR.
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. (2002)
J. Virol. 77, 1337-1346
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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.
K. W. Schjetne, K. M. Thompson, T. Aarvak, B. Fleckenstein, L. M. Sollid, and B. Bogen (2002)
Int. Immunol. 14, 1423-1430
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Human Immunodeficiency Virus Envelope (gp120) Binding to DC-SIGN and Primary Dendritic Cells Is Carbohydrate Dependent but Does Not Involve 2G12 or Cyanovirin Binding Sites: Implications for Structural Analyses of gp120-DC-SIGN Binding.
P. W.-P. Hong, K. B. Flummerfelt, A. de Parseval, K. Gurney, J. H. Elder, and B. Lee (2002)
J. Virol. 76, 12855-12865
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Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo.
T. B. H. Geijtenbeek, P. C. Groot, M. A. Nolte, S. J. van Vliet, S. T. Gangaram-Panday, G. C. F. van Duijnhoven, G. Kraal, A. J. M. van Oosterhout, and Y. van Kooyk (2002)
Blood 100, 2908-2916
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Restricted SIV Replication in Rhesus Macaque Lung Tissues During the Acute Phase of Infection.
C. L. Fuller, Y. K. Choi, B. A. Fallert, S. Capuano III, P. Rajakumar, M. Murphey-Corb, and T. A. Reinhart (2002)
Am. J. Pathol. 161, 969-978
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Quantitative Expression and Virus Transmission Analysis of DC-SIGN on Monocyte-Derived Dendritic Cells.
F. Baribaud, S. Pohlmann, G. Leslie, F. Mortari, and R. W. Doms (2002)
J. Virol. 76, 9135-9142
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The Mannose-Dependent Epitope for Neutralizing Antibody 2G12 on Human Immunodeficiency Virus Type 1 Glycoprotein gp120.
R. W. Sanders, M. Venturi, L. Schiffner, R. Kalyanaraman, H. Katinger, K. O. Lloyd, P. D. Kwong, and J. P. Moore (2002)
J. Virol. 76, 7293-7305
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The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of {alpha}1->2 Mannose Residues on the Outer Face of gp120.
C. N. Scanlan, R. Pantophlet, M. R. Wormald, E. Ollmann Saphire, R. Stanfield, I. A. Wilson, H. Katinger, R. A. Dwek, P. M. Rudd, and D. R. Burton (2002)
J. Virol. 76, 7306-7321
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DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology.
T. B. H. Geijtenbeek, A. Engering, and Y. van Kooyk (2002)
J. Leukoc. Biol. 71, 921-931
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Functional Evaluation of DC-SIGN Monoclonal Antibodies Reveals DC-SIGN Interactions with ICAM-3 Do Not Promote Human Immunodeficiency Virus Type 1 Transmission.
L. Wu, T. D. Martin, R. Vazeux, D. Unutmaz, and V. N. KewalRamani (2002)
J. Virol. 76, 5905-5914
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