Estefanía Ernesto, Flores Raquel, Gómez-Lozano Natalia, Aguilar Helena, López-Botet Miguel, Vilches Carlos
Servicio de Inmunología, Hospital Universitario Puerta de Hierro, San Martín de Porres 4, 28035 Madrid, Spain.
J Immunol. 2007 Apr 1;178(7):4402-10. doi: 10.4049/jimmunol.178.7.4402.
Human NK cells, by means of a repertoire of clonally distributed killer cell Ig-like receptors (KIR), survey the expression of individual self HLA class I molecules, which is often altered in infections and tumors. KIR2DL5 (CD158f) is the last identified KIR gene and, with KIR2DL4, constitutes a structurally divergent lineage conserved in different primate species. Research on KIR2DL5 has thus far been limited to its genetic aspects due to a lack of reagents to detect its product. We report here the identification and characterization of the receptor encoded by KIR2DL5 using a newly generated specific mAb that recognizes its most commonly expressed allele, KIR2DL5A*001. KIR2DL5 displays a variegated distribution on the surface of CD56(dim) NK cells. This contrasts with the expression pattern of its structural homolog KIR2DL4 (ubiquitous transcription, surface expression restricted to CD56(bright) NK cells) and resembles the profile of KIR recognizing classical HLA class I molecules. Like other MHC class I receptors, KIR2DL5 is also found in a variable proportion of T lymphocytes. KIR2DL5 is detected on the cell surface as a monomer of approximately 60 kDa that, upon tyrosine phosphorylation, recruits the Src homology region 2-containing protein tyrosine phosphatase-2 and, to a lesser extent, Src homology region 2-containing protein tyrosine phosphatase-1. Ab-mediated cross-linking of KIR2DL5 inhibits NK cell cytotoxicity against murine FcR+ P815 cells. KIR2DL5 is thus an inhibitory receptor gathering a combination of genetic, structural, and functional features unique among KIR, which suggests that KIR2DL5 plays a specialized role in innate immunity.
人类自然杀伤细胞通过一系列克隆分布的杀伤细胞免疫球蛋白样受体（KIR）来监测个体自身HLA I类分子的表达情况，这种表达在感染和肿瘤中常常发生改变。KIR2DL5（CD158f）是最后一个被鉴定的KIR基因，与KIR2DL4一起构成了在不同灵长类物种中保守的结构不同的谱系。由于缺乏检测其产物的试剂，迄今为止对KIR2DL5的研究仅限于其遗传方面。我们在此报告使用新产生的特异性单克隆抗体对KIR2DL5编码的受体进行的鉴定和表征，该抗体可识别其最常见表达的等位基因KIR2DL5A*001。KIR2DL5在CD56（dim）自然杀伤细胞表面呈现斑驳分布。这与其结构同源物KIR2DL4的表达模式形成对比（普遍转录，表面表达仅限于CD56（bright）自然杀伤细胞），并类似于识别经典HLA I类分子的KIR的特征。与其他MHC I类受体一样，KIR2DL5也存在于可变比例的T淋巴细胞中。KIR2DL5在细胞表面被检测为约60 kDa的单体，酪氨酸磷酸化后，它会募集含Src同源区2的蛋白酪氨酸磷酸酶-2，并在较小程度上募集含Src同源区2的蛋白酪氨酸磷酸酶-1。抗体介导的KIR2DL5交联抑制自然杀伤细胞对鼠FcR+ P815细胞的细胞毒性。因此，KIR2DL5是一种抑制性受体，具有KIR中独特的遗传、结构和功能特征组合，这表明KIR2DL5在先天免疫中发挥着特殊作用。
