DCIR interacts with ligands from both endogenous and pathogenic origin.
C-type lectins on dendritic cells function as antigen uptake and signaling receptors, thereby influencing cellular immune responses. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is one of the best-studied C-type lectin receptors expressed on DCs and its glycan specificity and functional requirements for ligand binding have been intensively investigated. The carbohydrate specificity of dendritic cell immunoreceptor (DCIR), another DC-expressed lectin, was still debated, but we have recently confirmed DCIR as mannose/fucose-binding lectin. Since DC-SIGN and DCIR may potentially share ligands, we set out to elucidate the interaction of DCIR with established DC-SIGN-binding ligands, by comparing the carbohydrate specificity of DCIR and DC-SIGN in more detail. Our results clearly demonstrate that DC-SIGN has a broader glycan specificity compared to DCIR, which interacts only with mannotriose, sulfo-Lewis(a), Lewis(b) and Lewis(a). While most of the tested DC-SIGN ligands bound DCIR as well, Candida albicans and some glycoproteins on some cancer cell lines were identified as DC-SIGN-specific ligands. Interestingly, DCIR strongly bound human immunodeficiency virus type 1 (HIV-1) gp140 glycoproteins, while its interaction with the well-studied DC-SIGN-binding HIV-1 ligand gp120 was much weaker. Furthermore, DCIR-specific ligands were detected on keratinocytes. Furthermore, the interaction of DCIR with its ligands was strongly influenced by the glycosylation of DCIR. In conclusion, we show that sulfo-Lewis(a) is a high affinity ligand for DCIR and that DCIR interacts with ligands from both pathogenic and endogenous origin of which most are shared by DC-SIGN.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; Danone Research, Centre for Specialized Nutrition, Wageningen, The Netherlands.
Karien
K
Bloem
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Ilona M
IM
Vuist
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Meike
M
van den Berk
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Elsenoor J
EJ
Klaver
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Irma
I
van Die
Danone Research, Centre for Specialized Nutrition, Wageningen, The Netherlands; Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
Léon M J
LM
Knippels
Danone Research, Centre for Specialized Nutrition, Wageningen, The Netherlands; Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
Johan
J
Garssen
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Juan J
JJ
García-Vallejo
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Sandra J
SJ
van Vliet
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: y.vankooyk@vumc.nl.
Yvette
Y
van Kooyk
D000818:Animals; D001426:Bacterial Proteins / Q000819:agonists; D002176:Candida albicans / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000819:agonists; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009844:Oligosaccharides / Q000819:agonists; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000819:agonists; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D054299:env Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C423004:CLEC4A protein, human; C514793:gp120 protein, Human immunodeficiency virus 1; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C116504:sulfo-Lewis(a)
C-type lectins; Dendritic cell; Glycan; Glycosylation; Pathogen and cancer