INHIBITION OF NATURAL-KILLER-CELL CYTOTOXICITY BY CELL GROWTH-RELATEDMOLECULES

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 tha t are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibro blast WFB cell line. In contrast, NK cells were cytotoxic to H-ras onc ogene-induced transformants of WFB, W14 and W31. FAGS analysis indicat ed that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thu s, this antigen may disappear concomitantly with cell growth and trans formation. Cho-l antigens were also expressed on other NK-resistant li nes, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibrobl ast HEPM. However, they were not expressed on NK-sensitive mouse YAC-I and H-ras transformant (Brash) of BALB3T3 cells, Furthermore, treatme nt of target cells with IFN-gamma clearly induced the cell surface exp ression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expres sion may correlate with target cell susceptibility to NK cells. Indeed , treatment of NK-resistant WFB as well as HEPM cells with F(ab')(2) f ragments of mAb Cho-1 resulted in the acquisition of susceptibility to Ng cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.