KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity
KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity
复制标题
DOI：
10.1182/blood-2004-03-0878
复制
发表时间：
2004-11-01
期刊：
影响因子：
20.3
通讯作者：
Cao, XT
中科院分区：
文献类型：
--
作者：
Han, YM;Zhang, MH;Cao, XT
自然杀伤（NK）细胞抑制性受体在调节靶细胞对自然杀伤的敏感性中起重要作用。在这里，我们报告的分子克隆和功能特性的一种新的NK细胞受体，KLRL 1，从人类和小鼠树突状细胞。KLRL 1是一种II型跨膜蛋白，具有基于免疫受体酪氨酸的抑制基序和C型凝集素样结构域。KLRL 1基因位于人类和小鼠NK基因复合体的中心区域，位于人类染色体12 p13和小鼠染色体6 F3上，与其他KLR基因相邻。KLRL 1优先在淋巴组织和免疫细胞中表达，包括NK细胞、T细胞、树突细胞和单核细胞或巨噬细胞。免疫印迹和荧光共聚焦显微镜分析表明，KLRL 1是一种膜相关的糖蛋白，它形成一个异源二聚体与一个尚未确定的合作伙伴。人类和小鼠KLRL 1都被预测含有假定的免疫受体酪氨酸基序（ITIM），免疫沉淀实验表明，KLRL 1与酪氨酸磷酸酶SHP-1（含SH 2结构域的蛋白酪氨酸磷酸酶1）和SHP-2。与其潜在的抑制功能一致，用人KLRL 1-Fc融合蛋白预处理靶细胞可增强NK介导的细胞毒性。综上所述，我们的研究结果表明，KLRL 1属于KLR家族，是一种新的抑制性NK细胞受体。(C)2004年，美国血液学会。
Natural killer (NK) cell inhibitory receptors play important roles in the regulation of target susceptibility to natural killing. Here, we report the molecular cloning and functional characterization of a novel NK cell receptor, KLRL1, from human and mouse dendritic cells. KLRL1 is a type II transmembrane protein with an immunoreceptor tyrosine-based inhibitory motif and a C-type lectinlike domain. The KLRL1 gene is located in the central region of the NK gene complex in both humans and mice, on human chromosome 12p13 and mouse chromosome 6F3, adjacent to the other KLR genes. KLRL1, is preferentially expressed in lymphoid tissues and immune cells, including NK cells,.T cells, dendritic cells, and monocytes or macrophages. Western blot and fluorescence confocal microscopy analyses indicated that KLRL1 is a membrane-associated glycoprotein, which forms a heterodimer with an as yet unidentified partner. Human and mouse KLRL1 are both predicted to contain putative immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoprecipitation experiments demonstrated that KLRL1 associates with the tyrosine phosphatases SHP-1 (SH2-domain-containing protein tyrosine phosphatase 1) and SHP-2. Consistent with its potential inhibitory function, pretreatment of target cells with human KLRL1-Fc fusion protein enhances NK-mediated cytotoxicity. Taken together, our results demonstrate that KLRL1 belongs to the KLR family and is a novel inhibitory NK cell receptor. (C) 2004 by The American Society of Hematology.