Department of Life Sciences, Sir Ernst Chain Building, Imperial College, London, UK.
Glycobiology. 2018 Aug 1;28(8):592-600. doi: 10.1093/glycob/cwy050.
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.
血液树突状细胞抗原 2（BDCA-2）是一种存在于浆细胞样树突状细胞表面的 C 型凝集素。它作为糖结合受体发挥作用，下调 I 型干扰素的产生，从而在寡糖介导的免疫调节中发挥作用。BDCA-2 的碳水化合物识别结构域选择性地结合半乳糖末端双天线聚糖。由于浆细胞样树突状细胞在富含糖蛋白的血浆环境中发挥作用，因此已经进行了实验以鉴定血液树突状细胞抗原 2 的内源性配体。印迹、亲和层析和蛋白质组学分析的组合表明，BDCA-2 的血清糖蛋白配体包括 IgG、IgA 和 IgM。与之前描述的 IgG 结合相比，IgA 和 IgM 具有更高的亲和力。不同免疫球蛋白亚类的结合常数低于这些糖蛋白配体的血清浓度，并大致成比例。与另一种主要的血清糖蛋白配体α2-巨球蛋白的结合与该蛋白酶抑制剂是否被激活无关。与所有这些糖蛋白配体的结合主要由每个分支带有末端半乳糖残基的双天线聚糖介导。糖蛋白配体的不同亲和力反映了这些半乳糖末端聚糖的数量以及它们在天然糖蛋白上的暴露程度不同。结果表明，正常的血清免疫球蛋白水平可能下调干扰素对进一步抗体产生的刺激。
