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 k_f and k_r at the cell surface and k_fe and k_re 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 k_f^′ and k_r^′ at the cell surface and k_fe^′ and k_re^′ in endosomes. B. Trafficking: Unbound IL-15Rs are constitutively internalized with rate k_endo. IL-15/IL-15Rβγ and IL-15/IL-15Rαβγ complexes are internalized with rate k_int. Soluble IL-15 and the high affinity ligand (IL-15/IL-15Rα) in the endosome recycle to the surface with rate k_rec. Intermediate and high affinity complexes are sorted for degradation with rate k_deg. C. Synthesis: The constitutive synthesis of IL-15Rβγ is represented by V_s. C_s and C_s′ induce the synthesis of IL-15Rβγ with rate k_syn and the synthesis of IL-15Rα with rate k_syn^′.