Interleukin-15 receptor (IL-15R) signaling via membrane-bound interleukin-15 (IL-15R)

Interleukin 15 receptor signaling via membrane-bound interleukin 15 refers to a specialized mode of cytokine presentation where interleukin 15 (IL‑15), a four-alpha helix bundle cytokine, is bound to its high-affinity alpha subunit receptor (IL‑15Rα) on the surface of presenting cells such as dendritic cells or monocytes. This complex is then "trans-presented" to neighboring natural killer (NK) cells and subsets of T lymphocytes that express the shared beta/gamma chain receptors. This mechanism enables highly localized, potent stimulation at immunological synapses. Membrane-bound IL-15 enhances expansion, survival, cytotoxicity, and memory formation in CD8+ T cells as well as NK cell development—functions critical for anti-tumor immunity but also implicated in autoimmunity when dysregulated. Therapeutic strategies leverage this biology by engineering infused T-cells with surface-expressed/membrane-bound IL-15 to boost their persistence and activity against cancer; conversely, blocking this axis can mitigate pathological lymphoproliferation. Drugs targeting this pathway include recombinant agonists that mimic trans-presentation to amplify anti-tumor responses in adoptive cellular therapies; antagonists are being developed for conditions where excessive signaling drives disease. Safety concerns focus on balancing robust immunity with risks like cytokine release syndrome or promotion of leukemias if not tightly regulated.[1][2][3][4][5][6]

Other names

IL-15 signalingInterleukin 15 pathwayIL-15/IL-15Rα complexMembrane-bound IL-15 trans-presentation

Agonists enhance immune effector function by stimulating proliferation, cytotoxicity, and survival of T cells/NK cells. Antagonists block excessive or pathogenic immune stimulation by inhibiting the interaction between IL‑15 and its receptor complex.