肿瘤坏死因子和白细胞介素2是对N-连接的寡糖特异的凝集素

TNF and IL-2,lectins with specificity fou N-linked oligosaccharides

采用固相结合试验证实:(1)rTNF-α和 rIL-2能以高度亲和力与多种含 N-连接寡糖的糖蛋白结合,其结合活性依赖于糖蛋白的糖基组分;(2)rTNF-α能识别各种类型的 N-连接糖链,而 rIL-2只能与高甘露糖型的 N-连接糖链结合;(3)甘露三糖特导地抑制 rTNF-α和 rIL-2与糖蛋白的结合;(4)rTNF-α和 rIL-2不能识别 O-连接的寡糖,由此表明,TNF 和 IL-2均为对 N-连接寡糖特异的凝集素,它们特异性识别的碳水化合物部位可能是 N-连接寡糖的核心结构.鉴于 N-连接的寡糖广泛存在于人类的分泌蛋白和膜糖蛋白,故单核,淋巴因子的碳水化合物结合活性在人类免疫反应调节中的作用将是一个值得探索的新领域.

Utilizing a solid phase binding assay,we have demonstrated that rTNF-α and rIL-2 bind with high affinity to the glycoproteins which contain N-linded oligosaccharides.The binding activities were critically dependent upon intact glycosylation.rTNF-α recognized various types of N-linked oligosaccharides,but rIL—2 could onlyxbind to the high mannose N—linkedoligosaccharides.Man (α1-6)(Man(α1-3))-Man-O-ethyl which is a component of the core of N-linked ligosaccharides, blocked the binding of the glycoproteins to rTNF-α and rIL-2 in the millimolar range,rTNF-α nd rIL-2 did not recognize the types of O-linked oligosaccharides.It is clear from our data that rTNF-α and rIL-2 should be considered as mammalian lectins which have the specificity for N-linked oligosaccharides.The carbohydrate binding site of the cytokines-specifically might be the core structure of N-linked oligosaccharides.In view of the N-linked ligosaccharides are commonly present on human secretory proteins and membrane glycoproteins,we propose that these observations open up entirely new avenues of research into the importance of carbohydrate recognition of cytokines in the regulation of the human immune response.