DC-SIGN, C1q, and gC1qR form a trimolecular receptor complex on the surface of monocyte-derived immature dendritic cells.
C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the 2 C1q receptors found on the DC surface-gC1qR and cC1qR-lack a direct conduit into intracellular elements, we postulated that the receptors must form complexes with transmembrane partners. In the present study, we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry, and immunoprecipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and both intact C1q and the globular portion of C1q bound to DC-SIGN. Whereas IgG reduced this binding significantly, the Arg residues (162-163) of the C1q-A chain, which are thought to contribute to the C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was reduced significantly in the absence of Ca(2+) and by preincubation of DC-SIGN with mannan, suggesting that C1q binds to DC-SIGN at its principal Ca(2+)-binding pocket, which has increased affinity for mannose residues. Antigen-capture ELISA and immunofluorescence microscopy revealed that C1q and gC1qR associate with DC-SIGN on blood DC precursors and immature DCs. The results of the present study suggest that C1q/gC1qR may regulate DC differentiation and function through the DC-SIGN-mediated induction of cell-signaling pathways.
Department of Medicine, Stony Brook University, Stony Brook, NY, USA.
Kinga K
KK
Hosszu
Alisa
A
Valentino
Uma
U
Vinayagasundaram
Rama
R
Vinayagasundaram
M Gordon
MG
Joyce
Yan
Y
Ji
Ellinor I B
EI
Peerschke
Berhane
B
Ghebrehiwet
D001667:Binding, Competitive; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D046912:Multiprotein Complexes / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D002118:Calcium; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D015922:Complement C1q; D037181:Lectins, C-Type; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C087299:C1QBP protein, human