C1q modulates the differentiation and function of cells committed to the monocyte-derived dendritic cell (DC) lineage. Because the two 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. Here we show that DC-SIGN, a C-type lectin expressed on DCs, binds directly to C1q, as assessed by ELISA, flow cytometry and immuno-precipitation experiments. Surface plasmon resonance analysis revealed that the interaction was specific, and intact C1q, as well as the globular portion of C1q, bound to DC-SIGN. While IgG significantly reduced the binding; the Arg residues (162-163) of the C1q-A-chain, considered to contribute to C1q-IgG interaction, were not required for C1q binding to DC-SIGN. Binding was significantly reduced in the absence of Ca(2+) and by pre-incubation 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. Thus the data suggest that C1q/gC1qR may regulate DC differentiation and function through DC-SIGN-mediated induction of cell signaling pathways.
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