The Molecular Dissection of Fcy Receptor Mediated Phagocytosis

Because hematopoietic cells express multiple Fcy receptor isoforms, the role of the individual Fcy receptors in phagocytosis has been difficult to define. Transfection of Fcy receptors into COS-l cells, which lack endogeneous Fey receptors but have phagocytic potential, has proved valuable for the study of individual Fcy receptor function. Using this model system, we have established that a single class of human Fcy receptor mediates phagocytosis in the absence of other Fc receptors and that isoforms from each Fcy receptor class mediate phagocytosis, although the requirements for phagocytosis differ. In investigating the relationship between structure and function for Fcy receptor mediated phagocytosis, the importance of the cytoplasmic tyrosines of the receptor or its associated y chain has been established. For example, two cytoplasmic YXXL sequences, in a configuration similar to the conserved tyrosine-containing motif found in Ig gene family receptors, are important for phagocytosis by the human Fcy receptor, FcyRIIA. FcyRl and FcyRlllA do not possess cytoplasmic tyrosines but transmit