FIGURE 3. Modeling of receptor assemblage in response to varying number of second chains.

A Matlab algorithm was used to calculate assemblage of IL-4 receptors on cell surfaces expressing only the Type-I IL-4 receptor. (a) IL-4Rα number was set to 1500. Second chain number was raised from 500 to 4500 and 2-dimensional equilibrium constant (K_a2) of IL-4Rα complexes for second chain were over a range from 0.01μm² to 1μm² as indicated. The ratio of assembled chains of highest (1.0 μm²) versus lowest (0.01 μm²) second chain K_a2 values was calculated for 100 and 1000 pg/ml at 500, 1500 and 4500 γc molecules per cell. (b) IL-4Rα number was set to 1500. 2-D equilibrium constant was varied from 1μm² to 0.01μm² and second chain number from 167 to 4500 per cell. Complexes assembled with 167 γc chains per cell at 100 and 1000 pg/ml of IL-4 or superkines at 2-D equilibrium constants of 1.0 μm², 0.1 μm² or 0.01 μm² are shown. (c) Phosphorylation of STAT6 in Ramos and U937 cells in response to super-4, IL-4 and KFR in the presence of anti-γc antibody (0, 5, or 50 μg/ml). Response in the absence of anti-γc was normalized to 100% and responses in the presence of anti-γc expressed as in relation to the normalized value. Data (mean and SEM) are from three independent experiments.