Interleukin-15 receptor alpha–Interleukin-15 complex (IL-15Rα–IL-15 complex)

The Interleukin-15 receptor alpha–Interleukin-15 complex (IL-15Rα–IL-15 complex) is a stable, high-affinity cytokine–receptor ligand complex central to immune system signaling. It differs from classic cytokine signaling by requiring *trans-presentation*: antigen-presenting cells or other “presenting” cells express IL-15 bound to IL-15Rα and deliver the complex to other immune cells (e.g., NK or CD8+ T cells) expressing IL-15Rβ and common γ chain, initiating signal transduction pathways that promote cell proliferation, survival, and cytotoxicity[2][4][5]. Clinical and biotechnological engineering of stabilized, recombinant IL-15–IL-15Rα complexes—sometimes called “superagonist” forms—is under active investigation for cancer immunotherapy and viral infection treatment, given their ability to robustly expand and activate NK and CD8+ T cells, but they pose therapeutic risks such as cytokine release syndrome and immune hyperactivation[3][4]. The complex is functionally distinct from the unbound cytokine or receptor, featuring unique regulation and pharmacology relevant both in health and disease[4][2][3].

Other names

IL-15–IL-15Rα complexIL-15:IL-15 receptor alpha complexIL-15 superagonist complexIL-15N72D:IL-15RαSu/Fc (biotechnologically modified forms)

Trans-presentation: IL-15Rα-presenting cell forms IL-15–IL-15Rα complex, interacts with target cells expressing IL-15Rβ and γ chain, triggering biological response. Superagonism: Stabilization and enhanced signaling by preformed IL-15–IL-15Rα complexes yields long circulating half-life and increased immune activation potency. JAK-STAT pathway activation, mTOR pathway activation on immune cells.