The goal of these studies is to analyze and examine the regulatory mechanisms implicated in ADCC (antibody-dependent cell mediated cytotoxicity) and specifically to determine the peptide sequence of the FcYRI involved in the regulation of the receptor in monocytes and cells of the monocytic lineage (U937). The initial aim will attempt to develop a biological system where to study the biochemical and functional consequences of introducing modifications on the FcYRI receptor by mutation of its coding sequences. The biological importance of this receptor is determined by its central role in monocyte and macrophage ADCC and clearance of immune complexes which is accomplished by phagocytosis and production of oxygen radicals such as nitric oxide, hydrogen peroxide and superoxide). Therefore, this receptor is a pivotal issue in the possible induction of adverse effects due to monoclonal antibody treatments. The understanding of the determinants that regulate this receptor, specifically the interaction with antibodies, will allow the design of monoclonal antibodies with the same efficacy but decreased toxicity, so that they can be safely used clinically.
