INTERACTION OF NATURAL-KILLER-CELLS WITH MHC CLASS-II - REVERSAL OF HLA-DR1-MEDIATED PROTECTION OF K562 TRANSFECTANT FROM NATURAL-KILLER CELL-MEDIATED CYTOLYSIS BY BREFELDIN-A

Major histocompatibility complex (MHC) class I antigens on tumour cell surfaces have been shown to modulate target susceptibility to natural killer (NK) cell-mediated lysis in some, although not all, systems in vestigated. MHC class II expression may also affect NK cell function, but the mechanism by which MHC class II antigen regulates NK cell acti vity has not been fully examined. In this study we induced HLA-DR1 exp ression by gene transfection into the classic NK-sensitive K562 cell l ine to study the interaction of NK cells with MHC class II molecules a nd the effect of brefeldin-A (BFA), an endogenous antigen-processing p athway blocker, on NK-target cell interaction. We demonstrated that th e expression of HLA-DR1 on the cell surface reduced K562 cell suscepti bility to NK lysis by peripheral blood monuclear cells and a NK cell l ine. The effect was demonstrable in prolonged (8 hr) cytotoxicity assa ys and was blocked by pretreatment of target cells with anti-HLA-DR an tibody. Treatment of K562 DR transfectant with BFA abrogated the resis tance of K562 transfectant to NK-mediated cytolysis. These findings in dicate that HLA class II molecules regulate NK cell function and targe t recognition, and suggest that endogenous peptides presented through MHC molecules are responsible for regulating NK cytolysis.