Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation
Figure 5
Representative diagram of intermediate and high affinity IL-15 receptor binding, trafficking and synthesis interactions.
Activated NK cells upregulate the expression of the high affinity α subunit of IL-15R. A. Binding: IL-15Rβγ associates with IL-15 with on and off rates kf and kr at the cell surface and kfe and kre in endosomes. All IL-15Rα are assumed to rapidly bind IL-15, forming the high affinity ligand for IL-15Rβγ. IL-15/IL-15Rα binds IL-15Rβγ with on and off rates kf′ and kr′ at the cell surface and kfe′ and kre′ in endosomes. B. Trafficking: Unbound IL-15Rs are constitutively internalized with rate kendo. IL-15/IL-15Rβγ and IL-15/IL-15Rαβγ complexes are internalized with rate kint. Soluble IL-15 and the high affinity ligand (IL-15/IL-15Rα) in the endosome recycle to the surface with rate krec. Intermediate and high affinity complexes are sorted for degradation with rate kdeg. C. Synthesis: The constitutive synthesis of IL-15Rβγ is represented by Vs. Cs and Cs′ induce the synthesis of IL-15Rβγ with rate ksyn and the synthesis of IL-15Rα with rate ksyn′.