Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors
Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors
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DOI：
10.1038/38028
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发表时间：
1997-09-04
期刊：
影响因子：
64.8
通讯作者：
Wiley, DC
中科院分区：
文献类型：
--
作者：
Fan, QR;Mosyak, L;Wiley, DC
缺乏I类主要组织相容性复合体（MHC）表达的异常细胞被一类称为自然杀伤（NK）细胞的淋巴细胞裂解（1）。这种裂解提供了针对下调MHC表达的病原体和肿瘤细胞的防御，以避免MHC限制性T细胞免疫应答。正常细胞逃避溶解，因为它们的MHC分子被抑制溶解的NK细胞抑制性受体识别（2）。已经在人类和小鼠中描述了几种这样的抑制性受体家族（综述于Ief. 2）。在人类白细胞抑制性受体家族中，单个p58成员对I类人类白细胞抗原（HLA）-C分子的子集具有特异性。人p58天然增殖细胞抑制性受体done 42识别HLA-Cw 4、-Cw 2和-Cw 6，但不识别HLA-Cw 3、-Cw 2、-Cw 7或-Cw 8，后者被p58增殖细胞抑制性受体克隆43识别（参考文献3）。我们已经确定了1.7埃分辨率的p58 NK细胞抑制性受体克隆42的X射线结构。该结构具有以锐角60度角定位的串联免疫球蛋白样结构域。在结构域之间手肘外侧上的环形成远离NK细胞表面突出的结合位点。这些结构域的拓扑结构及其相对于彼此的排列揭示了与造血受体家族的关系，并暗示了NK细胞中的信号传导机制。
Abnormal cells deficient in class I major histocompatibility complex (MHC) expression are lysed by a class of lymphocytes called natural killer (NK) cells(1). This lysis provides a defence against pathogens and tumour cells that downregulate MHC expression to avoid an MHC-restricted, T-cell immune response. Normal cells escape lysis because their MHC molecules are recognized by NK-cell inhibitory receptors, which inhibit lysis(2). Several such inhibitory receptor families have been described in humans and mice (reviewed in Ief. 2). In the human killer-cell inhibitory receptor family, individual p58 members are specific for a subset of class I human leukocyte antigen (HLA)-C molecules. The human p58 natural killer-cell inhibitory receptor done 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA-Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor receptor clone 43 (ref. 3). We have determined the X-ray structure of the p58 NK-cell inhibitory receptor clone 42 at 1.7-Angstrom resolution. The structure has tandem immunoglobulin-like domains positioned at an acute, 60-degree angle. Loops on the outside of the elbow between the domains form a binding site projected away from the NK-cell surface. The topology of the domains and their arrangement relative to each other reveal a relationship to the haematopoietic receptor family, with implications for the signalling mechanism in NK cells.