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Byron Goldstein
Theoretical Biology and Biophysics Group
Los Alamos National Laboratory


Modeling Immune Receptor Signaling and the Problem of Combinatorial Complexity

The process of signaling through cell surface receptors involves highly connected networks of interacting components. I will focus on the application of mathematical models to understanding signaling through immune recognition receptors which trigger a variety of immune responses. Simple models, like kinetic proofreading and serial engagement, which ignore the details of the signaling machinery, have provided considerable insight into how ligand-receptor binding properties affect signaling outcomes but are unable to make contact with the vast majority of cell signaling data. After reviewing these models and discussing their strengths and weaknesses, I will look at the problems that the modeler is confronted with when he or she tries to deal with the details of a signaling cascade. I illustrate with a model for the early signaling events mediated by the high affinity receptor for IgE, Fc eRI, a receptor that plays a key role in allergic reactions.




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