Lyman S D, Escobar S, Rousseau A M, Armstrong A, Fanslow W C
Immunex Corp., Seattle, Washington 98101, USA.
J Biol Chem. 2000 Feb 4;275(5):3431-7. doi: 10.1074/jbc.275.5.3431.
CD7 is a 40-kDa protein found primarily on T, NK, and pre-B cells; the function of the CD7 protein in the immune system is largely unknown. The K12 (SECTM1) protein was originally identified by its location just upstream of the CD7 locus. The K12 gene encodes a transmembrane protein of unknown function. In order to clone a K12-binding protein, we generated a soluble version of the human K12 protein by fusing its extracellular domain to the Fc portion of human IgG(1). Flow cytometry experiments showed that the K12-Fc fusion protein bound at high levels to both human T and NK cells. Precipitation experiments using K12-Fc on (35)S-radiolabeled NK cells lysates indicated that the K12 cognate was an approximately 40-kDa protein. A human peripheral blood T cell cDNA expression library was screened with the K12-Fc protein, and two independent, positive cDNA clones were identified and sequenced. Both cDNAs encoded the same protein, which was CD7. Thus, K12 and CD7 are cognate proteins that are located next to each other on human chromosome 17q25. Additionally, we have cloned the gene encoding the mouse homologue of K12, shown that it maps near the mouse CD7 gene on chromosome 11, and established that the mouse K12 protein binds to mouse, but not human, CD7. Mouse K12-Fc inhibited in a dose-dependent manner concanavalin A-induced proliferation, but not anti-TcRalpha/beta induced proliferation, of mouse lymph node T cells. Human K12-Fc stimulated the up-regulation of CD25, CD54, and CD69 on human NK cells in vitro.
CD7是一种主要在T细胞、自然杀伤细胞（NK细胞）和前B细胞上发现的40千道尔顿蛋白；CD7蛋白在免疫系统中的功能在很大程度上尚不清楚。K12（SECTM1）蛋白最初是因其位于CD7基因座上游的位置而被鉴定出来的。K12基因编码一种功能未知的跨膜蛋白。为了克隆一种与K12结合的蛋白，我们通过将人K12蛋白的细胞外结构域与人IgG(1)的Fc部分融合，生成了一种可溶性形式的人K12蛋白。流式细胞术实验表明，K12-Fc融合蛋白与人类T细胞和NK细胞都有高水平的结合。使用K12-Fc对(35)S放射性标记的NK细胞裂解物进行沉淀实验表明，K12的同源物是一种约40千道尔顿的蛋白。用人外周血T细胞cDNA表达文库筛选K12-Fc蛋白，鉴定并测序了两个独立的阳性cDNA克隆。两个cDNA都编码同一种蛋白，即CD7。因此，K12和CD7是同源蛋白，它们在人类17号染色体q25上彼此相邻。此外，我们克隆了编码小鼠K12同源物的基因，表明它定位在小鼠11号染色体上的小鼠CD7基因附近，并证实小鼠K12蛋白与小鼠CD7结合，但不与人CD7结合。小鼠K12-Fc以剂量依赖的方式抑制小鼠淋巴结T细胞的伴刀豆球蛋白A诱导的增殖，但不抑制抗T细胞受体α/β诱导的增殖。人K12-Fc在体外刺激人NK细胞上CD25、CD54和CD69的上调。
