Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation
Figure 6
The upregulation of IL-15Rα amplifies IL-15R signaling and modulates the steady state numbers of receptors, complexes, and ligands on the cell surface and in endosomes of dividing NK cells.
Numerical solutions of the computational model are depicted in two columns, showing receptor, intermediate affinity complex, and high affinity complex at the cell surface (A, C, E) and in endosomes (B, D, F). Model solutions were obtained from simulations where IL-15 concentration serially doubled from 3.9 ng/ml to 2000 ng/ml, represented by different lines with the arrow denoting increasing IL-15 concentration. G. The total number of signaling complexes at the cell surface is shown as the sum of intermediate and high affinity complexes. H. Fold change in total steady state cell surface IL-15/IL-15R complex numbers on dividing cells (with upregulation IL-15Rα) compared with quiescent NK cells (which express no appreciable IL-15Rα). The fold changes in this ratio at different IL-15 concentrations (serially doubled from 3.9 to 2000 ng/ml) are depicted by solid bars.