Abstract
Blood dendritic cell antigen 2 (BDCA-2) is a C-type lectin found on the surface of plasmacytoid dendritic cells. It functions as a glycan-binding receptor that downregulates the production of type I interferons and thus plays a role in oligosaccharide-mediated immunomodulation. The carbohydrate recognition domain in BDCA-2 binds selectively to galactose-terminated bi-antennary glycans. Because the plasmacytoid dendritic cells function in a plasma environment rich in glycoproteins, experiments have been undertaken to identify endogenous ligands for blood dendritic cell antigen 2. A combination of blotting, affinity chromatography and proteomic analysis reveals that serum glycoprotein ligands for BDCA-2 include IgG, IgA and IgM. Compared to binding of IgG, which was previously described, IgA and IgM bind with higher affinity. The association constants for the different subclasses of immunoglobulins are below and roughly proportional to the serum concentrations of these glycoprotein ligands. Binding to the other main serum glycoprotein ligand, α2-macroglobulin, is independent of whether this protease inhibitor is activated. Binding to all of these glycoprotein ligands is mediated predominantly by bi-antennary glycans in which each branch bears a terminal galactose residue. The different affinities of the glycoprotein ligands reflect the different numbers of these galactose-terminated glycans and their degree of exposure on the native glycoproteins. The results suggest that normal serum levels of immunoglobulins could downmodulate interferon stimulation of further antibody production.
Highlights
Blood dendritic cell antigen 2 (BDCA-2) is a specific marker for plasmacytoid dendritic cells circulating in the blood (Dzionek et al 2000, 2001)
Glycan array analysis, binding competition studies and structural studies of the binding specificity of BDCA-2 indicated that the carbohydrate recognition domain (CRD) binds with highest affinity to galactose-terminated N-linked glycans (Jégouzo et al 2015)
Because IgG is known to bear a significant fraction of such glycans, it was suggested that IgG is a potential ligand for BDCA-2 in serum, and binding to IgG was demonstrated
Summary
Blood dendritic cell antigen 2 (BDCA-2) is a specific marker for plasmacytoid dendritic cells circulating in the blood (Dzionek et al 2000, 2001). These cells play a key role in response to both viral and bacterial antigens by providing a source of type I interferon (IFN), which stimulates direct antiviral functions and can enhance the activity of dendritic cells and T and B lymphocytes (Reizis et al 2011; Schraml and Reis e Sousa 2015; Swiecki and Colonna 2015). The BDCA-2 polypeptide is associated with the common Fc receptor γ
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