Figure 2: Different mechanisms of IL-15 action. (a): Low levels of secreted IL-15 can bind to high affinity trimeric receptors through a juxtacrine mechanism. (b): IL-15 binds to the high-affinity IL-15Rα chain within the endoplasmic reticulum and is then shuttled to the cell membrane as a complex. (c): IL-15Rα can trans-present IL-15 to an apposing IL-2R NK cell through cell contact. (d): The possibility of cis-presentation by IL-15Rα/IL-15 membrane complex to an IL-2Rβ/γ c heterodimer on the same NK cell is shown. (e): A soluble sushi domain-IL-15Rα bound to IL-15 can perform trans-presentation in a soluble form. (f): Soluble IL-15Rα extracellular domain generated by metalloprotease cleavage can bind soluble IL-15 and block its function.