ANTIGEN-MEDIATED IGE RECEPTOR AGGREGATION AND SIGNALING - A WINDOW ONCELL-SURFACE STRUCTURE AND DYNAMICS

The high-affinity receptor for immunoglobulin E, Fc epsilon RI, serves as an archtype for multisubunit immunoreceptors that mediate cell act ivation in response to foreign antigens. Antigen-mediated aggregation of this receptor at the surface of mast cells and basophils initiates a biochemical cascade that uses nonreceptor tyrosine kinases as key pa rticipants in the earliest steps of this signal transduction process. Cross-linking of Fc epsilon RI with ligands of well-defined structure and valency has revealed detailed information about the fundamental re quirements for functionally active receptor aggregates. Cross-linking- dependent changes in the interaction of these receptors with other cel lular components have been characterized with biochemical and biophysi cal methods to develop a more complete view of signal initiation. Rece nt evidence suggests that this process involves the interaction of agg regated Fc epsilon RI with specialized plasma membrane domains that ma y localize important signaling molecules in the vicinity of aggregated receptors. Although these various studies were aimed toward understan ding the operation of one cell surface receptor, they provide new insi ghts into plasma membrane structure and dynamics that are generally re levant to the function of most nucleated mammalian cells.