Kanki K, Torigoe T, Hirai I, Sahara H, Kamiguchi K, Tamura Y, Yagihashi A, Sato N
Department of Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Microbiol Immunol. 2000;44(12):1051-61. doi: 10.1111/j.1348-0421.2000.tb02602.x.
The nature of target molecules of natural killer (NK) cell-mediated lysis remains to be elucidated. As we previously reported, mAb 109 recognizes one of the tumor-associated antigens, designated as 109 antigen (Ag), expressed on the cell surface of rat fibrosarcomas W31 and W14, which are transformants of WFB (rat fetal fibroblast cell line) with H-ras oncogene. 109Ag was thought to be a target structure of NK cells since mAb 109 inhibited NK cell-mediated lysis against W31 and W14. Here, we demonstrate by molecular cloning that 109Ag is identical to rat CD44. Immunoprecipitation and immunoblotting studies also showed that mAb 109 and anti-rat CD44 mAb OX-50 recognize the same protein of W31 cell lysates with an 86 kDa molecular size. CD44 was suggested to be a target structure of NK cell-mediated lysis; however, rat CD44 cDNA transfection alone into CD44 null cell lines did not result in up-regulation of target cell susceptibility to NK cell-mediated lysis. Our results therefore indicated that CD44 may play a crucial role as one of the target structures in our rat fibrosarcoma system though the cell surface expression of CD44 alone does not affect NK susceptibility of the target cells.
自然杀伤(NK)细胞介导的细胞裂解的靶分子的性质仍有待阐明。正如我们之前报道的,单克隆抗体109识别一种肿瘤相关抗原,命名为109抗原(Ag),其在大鼠纤维肉瘤W31和W14的细胞表面表达,这两种肉瘤是WFB(大鼠胎儿成纤维细胞系)用H-ras癌基因转化而来的。109Ag被认为是NK细胞的靶结构,因为单克隆抗体109抑制了NK细胞介导的对W31和W14的细胞裂解。在此,我们通过分子克隆证明109Ag与大鼠CD44相同。免疫沉淀和免疫印迹研究还表明,单克隆抗体109和抗大鼠CD44单克隆抗体OX-50识别W31细胞裂解物中相同的蛋白质,其分子大小为86 kDa。CD44被认为是NK细胞介导的细胞裂解的靶结构;然而,单独将大鼠CD44 cDNA转染到CD44缺失的细胞系中并没有导致靶细胞对NK细胞介导的细胞裂解的敏感性上调。因此,我们的结果表明,在我们的大鼠纤维肉瘤系统中,CD44可能作为靶结构之一发挥关键作用,尽管单独的CD44细胞表面表达并不影响靶细胞对NK细胞的敏感性。