Kiyohara T, Dennis J W, Roder J C
Cell Immunol. 1987 May;106(2):223-33. doi: 10.1016/0008-8749(87)90166-3.
The determinants of tumor cell susceptibility to NK cell-mediated cytolysis were analyzed in a two stage model. The binding of tumor cells to NK effectors was measured by target-effector conjugation and cold target competition in 51Cr-release assays, whereas triggering was measured by assaying phospholipid methylation in NK cells stimulated by intact targets. Representative targets could be grouped into three phenotypes based on the data. Those such as YAC 1.2 could bind and trigger NK cells whereas the mutagenized variant, YAC 6.28.8, could bind but was unable to trigger NK cells and therefore resisted lysis. The third phenotype was represented by HL-60 which could neither bind nor trigger NK cells and was therefore completely NK resistant. The oligosaccharide nature of the triggering molecules was demonstrated by showing that purified, high mannose containing, asparagine-linked oligosaccharides from tumor cell targets were potent stimulators of NK transmethylation at submicromolar levels. Tunicamycin pretreatment of target cells inhibited their triggering capacity but not their NK binding function. These results suggest a double restriction in NK specificity involving two independent but sequential stages in recognition represented in binding and triggering by asn-linked oligosaccharides on the tumor cell surface.
在一个两阶段模型中分析了肿瘤细胞对自然杀伤（NK）细胞介导的细胞溶解的敏感性决定因素。在51Cr释放试验中，通过靶细胞-效应细胞结合和冷靶竞争来测量肿瘤细胞与NK效应细胞的结合，而通过检测完整靶细胞刺激的NK细胞中的磷脂甲基化来测量触发。根据数据，代表性的靶细胞可分为三种表型。像YAC 1.2这样的靶细胞能够结合并触发NK细胞，而诱变变体YAC 6.28.8能够结合但无法触发NK细胞，因此抵抗裂解。第三种表型由HL-60代表，它既不能结合也不能触发NK细胞，因此对NK细胞完全耐药。通过表明来自肿瘤细胞靶标的纯化的、含高甘露糖的天冬酰胺连接寡糖在亚微摩尔水平上是NK转甲基化的有效刺激剂，证明了触发分子的寡糖性质。衣霉素预处理靶细胞会抑制其触发能力，但不会抑制其NK结合功能。这些结果表明NK特异性存在双重限制，涉及识别中的两个独立但相继的阶段，表现为肿瘤细胞表面天冬酰胺连接寡糖的结合和触发。
