ABSTRACT

The question of what antigenic determinants on target cells are recognized by NK cells has been complicated by the fact that NK cells may interact with their targets via two entirely different mechanisms. One mechanism involves the native NK receptor, assayed by in vitro cytotoxicity, while the other involves the participation of Fc receptors for IgG. The latter mechanism is called antibody dependent cell mediated cytotoxicity (ADCC) and can be assayed in vitro by incubating NK effector cells with targets in the presence of antitarget cell antibody. Previous experiments had suggested that NK cells and K cells that are responsible for ADCC of nucleated targets are one and the same cell type. For instance it was reported that patients with the Chediak-Higashi syndrome are both NK deficient and lack ADCC activity.18 Moreover, it was known from single-cell cytolytic assays that one effector cell may simultaneously lyse a target in an ADCC reaction and lyse another target in the absence of target cell specific antibody.I9 It is, therefore, not surprising that our cloned NK cells express ADCC activity.20 Target cells that lyse poorly in the presence of NK cells may lyse much better in the presence of target cell specific antibody of IgG but not of IgM isotype. It is, therefore, clear that antibody bound via the Fc receptor to the NK effector may serve as an antigen receptor in the lytic reaction. In recent studies we have shown that the mechanism of acute bone marrow allograft rejection involves NK cells6 and that the specificity of this rejection depends on the presence of target cell specific immunoglobulin in the graft recipient." This suggests that NK mediated ADCC indeed plays a physiological role in vivo.