Program
MSC6b | |
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Byron Goldstein | |
Los Alamos National Laboratory | |
Title | The Role of Serial Engagement in Mast Cell Signaling |
Abstract | The terms serial triggering and serial engagement entered the immunological lexicon when Valitutti et al. (1) reported that within the contact area between an antigen presenting cell and a T cell a few antigenic peptides bound to major histocompatibility complex mediated the internalization of hundreds of TCR receptors (TCRs). Although there has been a considerable effort to unravel the role of serial engagement of TCRs in activating T cells, the role of serial engagement of other multi-chain immune recognition receptors in cell activation has been ignored. I will review the roles that valence and receptor density play in determining the mean time for dissociation of multivalent ligands from cell surfaces and then present new results that allow us to estimate the number of receptors a single multivalent ligand can serial engage and the rate at which this engagement occurs. Finally, I will present results that use a detailed model of the early events triggered by bivalent ligands that aggregate receptors (FceRI) on mast cells (2). By simulating signaling induced by bivalent ligands that serial engage receptors at different rates while undergoing the same degree of kinetic proofreading, we can assess the role of serial engagement in mast cell signaling. 1. Valitutti, S., S. Muller, M.Cella, E. Padovan, and A. Lanzavecchia. Serial triggering on many T-cell receptors by a few peptide-MHC complexes. 1995. Nature, 275:148-151. 2.Faeder, J. R., W. S. Hlavacek, I. Reischl, M. L. Blinov, H. Metzger, A. Redondo, C. Wofsy and B. Goldstein. 2003. Investigation of early events in FceRI-mediated signaling using a detailed mathematical model. J. Immunol. 170:3769-2781. |
Location | Woodward 6 |