A disulfide-linked natural killer cell receptor dimer has higher affinity for HLA-C than wild-type monomer.
A disulfide-linked natural killer cell receptor dimer has higher affinity for HLA-C than wild-type monomer.
复制标题
二硫键连接的自然杀伤细胞受体二聚体对 HLA-C 的亲和力比野生型单体更高。
DOI：
10.1002/1521-4141(200009)30:9
复制
发表时间：
2000
影响因子：
5.4
通讯作者：
Wiley,DC
中科院分区：
文献类型：
--
作者：
Fan,QR;Long,EO;Wiley,DC
自然杀伤（NK）细胞表面的抑制性受体识别靶细胞上的特异性MHC I类分子并阻止NK细胞裂解靶细胞。杀伤细胞免疫球蛋白相关受体（KIR），KIR 2D，发现于人类，特异性地与多态性HLA-C分子相互作用。抑制性受体KIR 2DL 1的晶体结构揭示了与造血受体家族的关系，表明KIR 2D分子的信号传导机制可能类似于造血受体的信号传导机制，并且涉及KIR 2D二聚化。我们通过在受体的C末端茎区引入游离半胱氨酸，设计了KIR 2DL 1的二硫键连接二聚体。二硫键连接的KIR 2DL 1二聚体以一个二聚体与一个HLA-Cw 4分子的摩尔比与HLA-Cw 4结合。此外，共价连接的KIR 2DL 1二聚体比野生型单体更紧密地结合HLA-Cw 4，表明发生了第二次结合事件，增加了KIR二聚体对HLA-C的总体亲和力。
Inhibitory receptors on the surface of natural killer (NK) cells recognize specific MHC class I molecules on target cells and prevent the target cell lysis by NK cells. The killer cell immunoglobulin‐related receptors (KIR), KIR2D, found in human, specifically interact with polymorphic HLA‐C molecules. The crystal structure of the inhibitory receptor, KIR2DL1, revealed a relationship to the hematopoietic receptor family, suggesting that the signaling mechanism of KIR2D molecules may resemble that of the hematopoietic receptors, and involve KIR2D dimerization. We have engineered a disulfide‐linked dimer of KIR2DL1 by introducing a free cysteine at the C‐terminal stem region of the receptor. The disulfide‐linked KIR2DL1 dimer binds to HLA‐Cw4 at a molar ratio of one dimer to one HLA‐Cw4 molecule. Furthermore, the covalently‐linked KIR2DL1 dimer binds more tightly to HLA‐Cw4 than the wild‐type monomer, suggesting the occurrence of a second binding event that increases the overall affinity of KIR dimer for HLA‐C.