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Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2
Glycobiology ( IF 4.3 ) Pub Date : 2018-06-11 , DOI: 10.1093/glycob/cwy050
Jong-Won Kim 1 , James Budzak 1 , Yu Liu 1 , Sabine A F Jégouzo 1 , Kurt Drickamer 1 , Maureen E Taylor 1
Affiliation  

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.

中文翻译:

免疫调节受体血液树突状细胞抗原 2 血清糖蛋白配体的鉴定

血液树突状细胞抗原 2 (BDCA-2) 是一种在浆细胞样树突状细胞表面发现的 C 型凝集素。它作为聚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 中的碳水化合物识别结构域选择性地结合半乳糖封端的双触角聚糖。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,因此进行了实验来鉴定血液树突状细胞抗原 2 的内源配体。结合印迹、亲和层析和蛋白质组分析表明 BDCA-2 的血清糖蛋白配体包括 IgG 、IgA 和 IgM。与之前描述的 IgG 的结合相比,IgA 和 IgM 的结合亲和力更高。免疫球蛋白不同亚类的关联常数低于这些糖蛋白配体的血清浓度,并且大致与这些糖蛋白配体的血清浓度成比例。与另一种主要血清糖蛋白配体α 2 -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双触角聚糖介导,其中每个分支都带有末端半乳糖残基。糖蛋白配体的不同亲和力反映了这些半乳糖封端聚糖的不同数量及其对天然糖蛋白的暴露程度。结果表明,正常的血清免疫球蛋白水平可以下调干扰素对进一步抗体产生的刺激。
更新日期:2018-06-11
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