Parameters determining the stimulatory capacity of the type I Fc epsilon-receptor

Several experiments and theoretical considerations aimed at obtaining the parameters which determine the capacity of type I Fc epsilon-receptors to stimulate the secretion of mast cells are reviewed. Earlier studies have established that secretion requires Fc epsilon RI clustering at least two dimers. The roles of such clusters lifetimes and configuration requires a detailed and quantitative analysis of Fc epsilon RI clustering and stimulus secretion. Different approaches to these issues are described and discussed. We especially address the relevance of the general concept of kinetical proof reading (T.W. McKeithan, Proc. Natl. Acad. Sci. USA 92 (1995) 5042) which is based on the assumption that the stimulating receptors must stay in an active state sufficiently long to bridge the time interval between initiation and termination of cell activation. For mast cells which generally secrete upon clustering of type I Fc epsilon-receptors, this implies that effective stimulation requires a sufficiently long lifetime of such clusters. This notion is corroborated by results obtained from several experiments performed in the last 20 years which are briefly described and compared in this review.