Fc Receptors on Natural Killer Cells

Cytotoxicity and cytokine production represent the two major functional effects that follow interaction of natural killer (NK) cells with a variety of target cells (reviewed in Trinchieri 1989). The receptor(s) involved in binding/recognition of target cells sensitive to spontaneous cytotoxicity (i.e., that mediated by NK cells from healthy nonimmunized individuals against nonsensitized targets) remain elusive. Target cells not bound spontaneously by NK cells can be recognized if coated with intact IgG antibodies, and NK cell recognition of these particulate immune complexes triggers antibody-dependent cell-mediated cytotoxicity (ADCC), following binding to receptors for the Fc portion of Ig (FcR) expressed on these cells. In these conditions, analogous to what is observed upon target cell recognition, cytokine expression and production are also induced with fast kinetics, and the same effects are elicited with monoclonal antibodies (mAb) to these molecules. Recognition of target cells that express major histocompatibility complex (MHC) class I antigens can modulate both FcR-dependent and FcR-independent NK cell activation, indicating that common biochemical events are elicited in both cases.