The C-type lectin L-SIGN differentially recognizes glycan antigens on egg glycosphingolipids and soluble egg glycoproteins from Schistosoma mansoni
The C-type lectin L-SIGN differentially recognizes glycan antigens on egg glycosphingolipids and soluble egg glycoproteins from Schistosoma mansoni
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DOI：
10.1093/glycob/cwm073
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发表时间：
2007-10-01
期刊：
影响因子：
4.3
通讯作者：
van Die, Irma
中科院分区：
文献类型：
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作者：
Meyer, Sandra;Tefsen, Boris;van Die, Irma
抗原呈递细胞对病原体衍生的碳水化合物成分的识别是诱导保护性免疫的重要步骤。在此我们研究了L - SIGN（肝脏/淋巴结特异性细胞间黏附分子 - 3结合非整合素）与曼氏血吸虫卵源性聚糖抗原的相互作用，L - SIGN是一种在人肝窦内皮细胞上作为抗原受体发挥作用的C型凝集素。我们的数据表明，L - SIGN既能结合血吸虫可溶性虫卵抗原（SEA），也能结合卵鞘糖脂，并且能够介导表达L - SIGN的细胞对SEA的内化。用内切糖苷酶H处理SEA后，SEA的结合和内化作用显著降低，而去岩藻糖基化既不影响结合也不影响内化。这些数据表明L - SIGN主要与SEA的寡甘露糖型N - 聚糖相互作用。相反，去岩藻糖基化后与卵鞘糖脂的结合完全消失。我们的数据显示，L - SIGN与一个含有岩藻糖基化种类的鞘糖脂组分结合，其组成经质谱分析为己糖、己糖胺（5 - 7）脱氧己糖（3 - 6）神经酰胺，如质谱所证明。结合岩藻糖基化路易斯抗原的L - SIGN“功能获得”突变体Ser363Val并不与这个岩藻糖基化卵鞘糖脂组分结合，这表明L - SIGN在结合卵鞘糖脂的岩藻糖和路易斯抗原时分别呈现不同的模式。分子模拟研究表明，L - SIGN与相应岩藻糖基化卵鞘糖脂寡糖的优先结合模式涉及非还原端的一个岩藻糖α1 - 3半乳糖胺β1 - 4（岩藻糖α1 - 3）N - 乙酰葡糖胺四糖。总之，我们的数据表明L - SIGN能识别血吸虫卵抗原内的寡甘露糖型N - 聚糖和多岩藻糖基化的碳水化合物基序，这证明L - SIGN具有广泛但特异的聚糖识别谱。
Recognition of pathogen-derived carbohydrate constituents by antigen presenting cells is an important step in the induction of protective immunity. Here we investigated the interaction of L-SIGN (liver/lymph node specific ICAM-3-grabbing nonintegrin), a C-type lectin that functions as antigen receptor on human liver sinusoidal endothelial cells, with egg-derived glycan antigens of the parasitic trematode Schistosoma mansoni. Our data demonstrate that L-SIGN binds both schistosomal soluble egg antigens (SEA) and egg glycosphingolipids, and can mediate internalization of SEA by L-SIGN expressing cells. Binding and internalization of SEA was strongly reduced after treatment of SEA with endoglycosidase H, whereas defucosylation affected neither binding nor internalization. These data indicate that L-SIGN predominantly interacts with oligomannosidic N-glycans of SEA. In contrast, binding to egg glycosphingolipids was completely abolished after defucosylation. Our data show that L-SIGN binds to a glycosphingolipid fraction containing fucosylated species with compositions of Hex, HexNAc(5-7)dHex(3-6)Cer, as evidenced by mass spectrometry. The L-SIGN "gain of function" mutant Ser363Val, which binds fucosylated Lewis antigens, did not bind to this fucosylated egg glycosphingolipid fraction, suggesting that L-SIGN displays different modes in binding fucoses of egg glycosphingolipids and Lewis antigens, respectively. Molecular modeling studies indicate that the preferred binding mode of L-SIGN to the respective fucosylated egg glycosphingolipid oligosaccharides involves a Fuc alpha 1-3GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc tetrasaccharide at the nonreducing end. In conclusion, our data indicate that L-SIGN recognizes both oligomannosidic N-glycans and multiply fucosylated carbohydrate motifs within Schistosoma egg antigens, which demonstrates that L-SIGN has a broad but specific glycan recognition profile.