| Structural highlights
Function
CD209_HUMAN Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. The receptor returns to the cell membrane surface and the pathogen-derived antigens are presented to resting T-cells via MHC class II proteins to initiate the adaptive immune response. Probably recognizes in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens, including HIV-1 gp120, HIV-2 gp120, SIV gp120, ebolavirus glycoproteins, cytomegalovirus gB, HCV E2, dengue virus gE, Leishmania pifanoi LPG, Lewis-x antigen in Helicobacter pylori LPS, mannose in Klebsiella pneumonae LPS, di-mannose and tri-mannose in Mycobacterium tuberculosis ManLAM and Lewis-x antigen in Schistosoma mansoni SEA.[1] [2] [3] [4] [5] [6] On DCs it is a high affinity receptor for ICAM2 and ICAM3 by binding to mannose-like carbohydrates. May act as a DC rolling receptor that mediates transendothelial migration of DC presursors from blood to tissues by binding endothelial ICAM2. Seems to regulate DC-induced T-cell proliferation by binding to ICAM3 on T-cells in the immunological synapse formed between DC and T-cells.[7] [8] [9] [10] [11] [12]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR.,Feinberg H, Mitchell DA, Drickamer K, Weis WI Science. 2001 Dec 7;294(5549):2163-6. PMID:11739956[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000 Mar 3;100(5):587-97. PMID:10721995
- ↑ Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 2000 Oct;1(4):353-7. PMID:11017109 doi:10.1038/79815
- ↑ Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V, van Kooyk Y. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 2002 Mar 1;168(5):2118-26. PMID:11859097
- ↑ Kwon DS, Gregorio G, Bitton N, Hendrickson WA, Littman DR. DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity. 2002 Jan;16(1):135-44. PMID:11825572
- ↑ Nobile C, Moris A, Porrot F, Sol-Foulon N, Schwartz O. Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN. J Virol. 2003 May;77(9):5313-23. PMID:12692233
- ↑ Appelmelk BJ, van Die I, van Vliet SJ, Vandenbroucke-Grauls CM, Geijtenbeek TB, van Kooyk Y. Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. J Immunol. 2003 Feb 15;170(4):1635-9. PMID:12574325
- ↑ Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000 Mar 3;100(5):587-97. PMID:10721995
- ↑ Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 2000 Oct;1(4):353-7. PMID:11017109 doi:10.1038/79815
- ↑ Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V, van Kooyk Y. The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol. 2002 Mar 1;168(5):2118-26. PMID:11859097
- ↑ Kwon DS, Gregorio G, Bitton N, Hendrickson WA, Littman DR. DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity. 2002 Jan;16(1):135-44. PMID:11825572
- ↑ Nobile C, Moris A, Porrot F, Sol-Foulon N, Schwartz O. Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN. J Virol. 2003 May;77(9):5313-23. PMID:12692233
- ↑ Appelmelk BJ, van Die I, van Vliet SJ, Vandenbroucke-Grauls CM, Geijtenbeek TB, van Kooyk Y. Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. J Immunol. 2003 Feb 15;170(4):1635-9. PMID:12574325
- ↑ Feinberg H, Mitchell DA, Drickamer K, Weis WI. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science. 2001 Dec 7;294(5549):2163-6. PMID:11739956 doi:http://dx.doi.org/10.1126/science.1066371
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