Receptors for IgG (FcR) are present on leukocytes effector of non-adaptive systems of defense against pathogenes, and they function as linking structures between the intra- and extracellular compartments. By binding specific immunoglobulins or antigen- antibody complexes, FcR allow the targeting of non-immune cells activities by the specific proteins of the immune response. FcR- ligand interaction and several lymphokines both variably modulate the functions of these cells in resistance to pathogens, and the surface expression of receptors for IgG and for other molecules (e.g. growth factors). Our data indicate that the interaction of membrane FcR (CD16 antigen) of natural killer (NK) cells with their specific ligand or with monoclonal anti-CD16 antibodies that mimic the ligand eventually results in either or both activation and inactivation of NK cells, as evidentiated by ultrastructural changes, novel mRNA transcription and modulation of both FcR- dependent and -independent functions. Our working hypothesis is that the low affinity FcR on NK cells act as signal-transducing structures upon interaction with their ligands. To test this, we will: a) determine the mechanism(s) by which FcR-ligand interactions impart activation signals to the cells at the molecular level, b) analyze the role of CD16 molecule as ligand- dependent ion channel, c) dissect the mechanism by which FcR- ligand interactions induce modulation of cytotoxic and proliferative potential of human NK cells. To define unifying or distinctive features of behaviour of FcR and FcR-dependent functions of different cells of the non-adaptive system of defense, we will compare the functional properties of FcR on NK cells with those of a similar FcR type on granulocytes. Experiments will also be performed to determine whether the high affinity FcR on monocytes and cytokine-activated granulocytes, like the CD16 molecule on NK cells and PMN.