Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation
Figure 7
Formation of high affinity receptor-ligand complexes facilitates exponential expansion of dividing NK cells.
A. The total steady state cell surface IL-15/IL-15R complex numbers in the high affinity binding model stimulate an exponential proliferative response, illustrated by plotting the fraction of maximal response vs. total Cs at the corresponding IL-15 concentrations. B. The maximum number of divisions calculated from the time elapsed since recruitment to cell division by the interdivision time for four different IL-15 concentrations. Solid lines represent model predictions, and filled circles represent the maximum detectable number of NK cell divisions obtained from independent experiments (9 ng/ml n = 3, 25 ng/ml n = 4, 50 ng/ml n = 2, and 75 ng/ml n = 3). The quality of prediction is represented by the normalized root mean squared deviation (NRMSD). The NRMSD of model prediction vs. experimental data are shown as percentages in the upper left of each graph. For reference, linear regression was performed for all four sets of experimental data, and the NRMSD values of the linear regressions were 9% (9 ng/ml), 10% (25 ng/ml), 14% (50 ng/ml), and 12% (75 ng/ml). C. Population mean division rate is estimated from the interdivision time for four IL-15 concentrations. White bars represent model predictions while black bars represent experimental data from the analysis of NK cell populations in 2–4 independent experiments.