Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells
Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells
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DOI：
10.1093/intimm/dxh246
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
van Kooyk, Y
中科院分区：
文献类型：
--
作者：
van Vliet, SJ;van Liempt, E;van Kooyk, Y
树突状细胞（DC）是维持外周对自身抗原耐受性和协调对外源抗原免疫反应的关键。由DC表达的C型凝集素识别抗原上的碳水化合物部分，所述碳水化合物部分可以被内化用于加工和呈递。关于自身抗原和病原体上被不同C型凝集素特异性识别的确切聚糖结构以及这种相互作用如何影响DC功能知之甚少。我们已经分析了碳水化合物的特异性的人C型凝集素巨噬细胞半乳糖型凝集素（MGL）使用聚糖微阵列分析，并确定了独家的特异性末端α和β-连接的GalNAc残基，天然存在的糖蛋白或鞘糖脂的一部分。含有末端GalNAc部分的特定聚糖结构，由人类蠕虫寄生虫曼氏血吸虫以及肿瘤抗原和神经节苷脂的子集表达，被鉴定为MGL的配体。我们的研究结果表明，DC表达的MGL在清除和耐受自我神经节苷脂，并在模式识别的肿瘤抗原和外来糖蛋白来自蠕虫寄生虫的内源性功能。
Dendritic cells (DCs) are key to the maintenance of peripheral tolerance to self-antigens and the orchestration of an immune reaction to foreign antigens. C-type lectins, expressed by DCs, recognize carbohydrate moieties on antigens that can be internalized for processing and presentation. Little is known about the exact glycan structures on self-antigens and pathogens that are specifically recognized by the different C-type lectins and how this interaction influences DC function. We have analyzed the carbohydrate specificity of the human C-type lectin macrophage galactose-type lectin (MGL) using glycan microarray profiling and identified an exclusive specificity for terminal alpha- and beta-linked GalNAc residues that naturally occur as parts of glycoproteins or glycosphingolipids. Specific glycan structures containing terminal GalNAc moieties, expressed by the human helminth parasite Schistosoma mansoni as well as tumor antigens and a subset of gangliosides, were identified as ligands for MGL. Our results indicate an endogenous function for DC-expressed MGL in the clearance and tolerance to self-gangliosides, and in the pattern recognition of tumor antigens and foreign glycoproteins derived from helminth parasites.