Biological Rule-Based Modeling of Experimental Cell Secretion Data

The allergic response in humans results from the crosslinking of IgE-Fc<; RI receptor complexes via the binding of IgE antibodies to antigens, which results in cell degranulation. The relationship between cell degranulation and antigen-antibody aggregation was investigated for the shrimp allergen Pen a 1. A biological rule-based model was developed to simulate aggregation of IgE antibodies and the Pen a 1 antigen. The forward rate constant and the crosslinking factor were varied to demonstrate how the model output changes as these model parameters are changed. It was found that the peak of the dose-response curve becomes greater and more defined as the crosslinking factor increases, and that the peak shifts to lower doses as the forward rate constant increases. Parameter scanning was performed to fit the model output to experimental cell secretion data obtained by collaborators, assuming a directly proportional relationship between the two quantities. Four concentrations of allergenspecific IgE were examined: 15 ng/mL, 30 ng/mL, 60 ng/mL, and 120 ng/mL. For each IgE concentration, nine doses of Pen a 1 were examined ranging from 0.0001 ng/mL to 10,000 ng/mL. The average aggregate size was used as the measure of aggregation to compare to the experimental data. It was found that the output of the biological rule-based model fit well to the cell degranulation data.