Inhibition of Natural Killer Cell Cytotoxicity by Cell Growth‐related Molecules

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‐γ 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‐I 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.