Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2.
Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2.
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DOI：
10.1093/glycob/cwy050
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发表时间：
2018-08-01
期刊：
影响因子：
4.3
通讯作者：
Taylor ME
中科院分区：
文献类型：
--
作者：
Kim JW;Budzak J;Liu Y;Jégouzo SAF;Drickamer K;Taylor ME
血树突状细胞抗原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。它作为一种聚糖结合受体，下调I型干扰素的产生，从而在低聚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与半乳糖末端双天线聚糖结合。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，已经开展了鉴定血液树突状细胞抗原内源性配体的实验2。结合印迹、亲和层析和蛋白质组学分析，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的结合具有更高的亲和力。不同亚类免疫球蛋白的结合常数如下，大致与这些糖蛋白配体的血清浓度成正比。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是由双触角聚糖介导的，其中每个分支具有末端半乳糖残基。糖蛋白配体的不同亲和力反映了这些半乳糖端聚糖的不同数量及其在天然糖蛋白上的暴露程度。结果表明，正常的血清免疫球蛋白水平可以下调干扰素刺激进一步的抗体产生。
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.
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DOI：
10.1074/jbc.m115.660613
发表时间：
2015-07-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jégouzo SA;Feinberg H;Dungarwalla T;Drickamer K;Weis WI;Taylor ME
通讯作者：
Taylor ME
影响因子：
4.4
作者：
Dzionek, A;Fuchs, A;Schmitz, J
通讯作者：
Schmitz, J
影响因子：
4.3
作者：
Jaehn, Peter S.;Zaenker, Kurt S.;Dzionek, Andrzej
通讯作者：
Dzionek, Andrzej
影响因子：
2.2
作者：
DEBEER, FC;PEPYS, MB
通讯作者：
PEPYS, MB
影响因子：
4.3
作者：
Powlesland AS;Hitchen PG;Parry S;Graham SA;Barrio MM;Elola MT;Mordoh J;Dell A;Drickamer K;Taylor ME
通讯作者：
Taylor ME