Jégouzo Sabine A F, Feinberg Hadar, Dungarwalla Tabassum, Drickamer Kurt, Weis William I, Taylor Maureen E
the Department of Life Sciences, Imperial College, London SW7 2AZ, United Kingdom.
From the Departments of Structural Biology and Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305 and.
J Biol Chem. 2015 Jul 3;290(27):16759-71. doi: 10.1074/jbc.M115.660613. Epub 2015 May 20.
Blood dendritic cell antigen 2 (BDCA-2; also designated CLEC4C or CD303) is uniquely expressed on plasmacytoid dendritic cells. Stimulation of BDCA-2 with antibodies leads to an anti-inflammatory response in these cells, but the natural ligands for the receptor are not known. The C-type carbohydrate recognition domain in the extracellular portion of BDCA-2 contains a signature motif typical of C-type animal lectins that bind mannose, glucose, or GlcNAc, yet it has been reported that BDCA-2 binds selectively to galactose-terminated, biantennary N-linked glycans. A combination of glycan array analysis and binding competition studies with monosaccharides and natural and synthetic oligosaccharides have been used to define the binding epitope for BDCA-2 as the trisaccharide Galβ1-3/4GlcNAcβ1-2Man. X-ray crystallography and mutagenesis studies show that mannose is ligated to the conserved Ca(2+) in the primary binding site that is characteristic of C-type carbohydrate recognition domains, and the GlcNAc and galactose residues make additional interactions in a wide, shallow groove adjacent to the primary binding site. As predicted from these studies, BDCA-2 binds to IgG, which bears galactose-terminated glycans that are not commonly found attached to other serum glycoproteins. Thus, BDCA-2 has the potential to serve as a previously unrecognized immunoglobulin Fc receptor.
血液树突状细胞抗原2（BDCA-2；也称为CLEC4C或CD303）仅在浆细胞样树突状细胞上表达。用抗体刺激BDCA-2会导致这些细胞产生抗炎反应，但该受体的天然配体尚不清楚。BDCA-2细胞外部分的C型碳水化合物识别结构域包含一个典型的C型动物凝集素特征基序，该凝集素可结合甘露糖、葡萄糖或N-乙酰葡糖胺，但据报道BDCA-2可选择性结合半乳糖末端的双天线N-连接聚糖。聚糖阵列分析以及与单糖、天然和合成寡糖的结合竞争研究相结合，已将BDCA-2的结合表位定义为三糖Galβ1-3/4GlcNAcβ1-2Man。X射线晶体学和诱变研究表明，甘露糖与C型碳水化合物识别结构域特征性的主要结合位点中的保守Ca(2+)相连，N-乙酰葡糖胺和半乳糖残基在主要结合位点相邻的宽浅沟中产生额外相互作用。正如这些研究所预测的，BDCA-2与IgG结合，IgG带有半乳糖末端聚糖，而这些聚糖在其他血清糖蛋白上并不常见。因此，BDCA-2有可能作为一种以前未被认识的免疫球蛋白Fc受体。
