Yokoyama W M, Ryan J C, Hunter J J, Smith H R, Stark M, Seaman W E
Rosalind Russell Arthritis Research Laboratory, Department of Medicine, University of California, San Francisco 94143.
J Immunol. 1991 Nov 1;147(9):3229-36.
NK cells lyse tumor cells and virally infected cells, but the molecular basis for this phenomenon has not been defined. A mAb specific for the rat cell surface molecule, NKR-P1, stimulates rat NK cell lytic activity and is reactive with all rat NK cells, suggesting that this molecule may play a significant role in NK cell function. We have previously described another NK cell-specific Ag, Ly-49, that belongs to a family of cross-hybridizing genes on distal mouse chromosome 6. The rat NKR-P1 Ag shares several features with the mouse Ly-49 Ag, including selective cell surface expression on NK cells, homology to the C-type lectins, expression as a type II integral membrane protein, and disulfide-linked homodimeric structure. To further examine the relationship of NKR-P1 to Ly-49, we have cloned the cDNA encoding a mouse homologue of NKR-P1 (mNKR-P1). The mouse and rat NKR-P1-deduced polypeptide sequences are highly conserved, suggesting a similar tertiary structure. By examination of DNA from informative recombinant inbred mice with Southern blot analysis, we have determined that mNKR-P1 is encoded by a distinct gene that is genetically linked to the Ly-49 locus, lying within 0.5 centi-Morgan (cM) of Ly-49. Although the deduced amino acid sequences of mNKR-P1 and Ly-49 reveal that these proteins are structurally similar, they are only 24% identical at the amino acid level and the cDNA sequences do not demonstrate significant nucleotide homology. Our studies suggest that we have identified a region on mouse chromosome 6 that includes distinct NK-specific genes that encode structurally related proteins (type II integral membrane proteins, C-type lectin super-gene family) but which demonstrate considerable heterogeneity. We have termed this genetic region the NK complex.
自然杀伤（NK）细胞可裂解肿瘤细胞和病毒感染细胞，但这一现象的分子基础尚未明确。一种针对大鼠细胞表面分子NKR-P1的单克隆抗体（mAb）可刺激大鼠NK细胞的裂解活性，且与所有大鼠NK细胞发生反应，这表明该分子可能在NK细胞功能中发挥重要作用。我们之前曾描述过另一种NK细胞特异性抗原Ly-49，它属于小鼠6号远端染色体上交叉杂交基因家族。大鼠NKR-P1抗原与小鼠Ly-49抗原有几个共同特征，包括在NK细胞上的选择性细胞表面表达、与C型凝集素的同源性、作为II型整合膜蛋白的表达以及二硫键连接的同型二聚体结构。为了进一步研究NKR-P1与Ly-49的关系，我们克隆了编码NKR-P1小鼠同源物（mNKR-P1）的cDNA。小鼠和大鼠NKR-P1推导的多肽序列高度保守，表明其三级结构相似。通过对信息性重组近交小鼠的DNA进行Southern印迹分析，我们确定mNKR-P1由一个与Ly-49基因座遗传连锁的独特基因编码，位于Ly-49的0.5厘摩（cM）范围内。尽管mNKR-P1和Ly-49推导的氨基酸序列表明这些蛋白质在结构上相似，但它们在氨基酸水平上仅24%相同，且cDNA序列未显示出显著的核苷酸同源性。我们的研究表明，我们在小鼠6号染色体上鉴定出了一个区域，该区域包含不同的NK特异性基因，这些基因编码结构相关的蛋白质（II型整合膜蛋白，C型凝集素超基因家族），但显示出相当大的异质性。我们将这个遗传区域称为NK复合体。
