Tamura Y, Takashima S, Cho J M, Qi W, Kamiguchi K, Torigoe T, Takahashi S, Hirai I, Sato N, Kikuchi K
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Jpn J Cancer Res. 1996 Jun;87(6):623-30. doi: 10.1111/j.1349-7006.1996.tb00269.x.
Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H-ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H-ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-gamma clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')2 fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.
已知靶细胞上的某些MHC I类分子可抑制自然杀伤细胞（NK细胞）的细胞毒性作用。通过使用单克隆抗体（mAb）Cho-1，我们发现了与200 kDa和40 kDa抗原非共价结合的抑制性非MHC I类细胞表面分子。聚肌胞苷酸（Poly I-C）诱导的大鼠NK细胞对大鼠胎儿来源的成纤维细胞WFB细胞系无细胞毒性。相反，NK细胞对H-ras癌基因诱导的WFB转化细胞W14和W31具有细胞毒性。荧光激活细胞分选（FACS）分析表明，mAb Cho-1与WFB细胞反应，但不与W14和W31细胞反应。因此，这种抗原可能随着细胞生长和转化而同时消失。Cho-1抗原也在其他NK抗性细胞系上表达，如小鼠BALB3T3成纤维细胞、EL-4淋巴瘤细胞和人成纤维细胞HEPM。然而，它们在NK敏感的小鼠YAC-1细胞和BALB3T3细胞的H-ras转化细胞（Brash）上不表达。此外，用γ干扰素处理靶细胞可明显诱导Cho-1抗原在细胞表面的表达，并赋予靶细胞对NK细胞溶解的抗性。这些数据强烈表明，Cho-1抗原的表达可能与靶细胞对NK细胞的敏感性相关。事实上，用mAb Cho-1的F(ab')2片段处理NK抗性的WFB细胞以及HEPM细胞，可使其获得对NK细胞溶解的敏感性。Cho-1抗原可能是调节细胞NK抗性的新分子。
