Interleukin-15 receptor (IL-15R) complex (IL-15R)

The interleukin-15 receptor (IL-15R) complex is a heterotrimeric cytokine receptor composed of three subunits: a high-affinity, ligand-specific alpha subunit (IL-15Rα), a beta subunit (IL-2Rβ/CD122) shared with the interleukin-2 receptor, and a common gamma chain (γc, CD132) shared with several other cytokine receptors[2][3][1][5]. IL-15 primarily signals via "trans-presentation," in which IL-15 bound to IL-15Rα on one cell is presented to the IL-2Rβ/γc dimer on an adjacent immune cell (typically NK or CD8+ T cells), thereby initiating JAK1/JAK3-STAT3/STAT5 and PI3K/mTOR pathway activation[2][1][3]. IL-15R-mediated signaling induces lymphocyte proliferation, survival, and activation, playing key roles in anti-viral immunity, tumor surveillance, and the development/survival of NK and memory CD8+ T cells[2][1]. Dysregulation is implicated in various cancers, autoimmune disorders, and inflammation. Therapeutically, targeting IL-15R can be achieved through administration of IL-15 agonists (to boost immunity) or antagonists (to suppress pathological immune activation)[2][1]. The unique structure and biology of the IL-15R complex, including its specialized alpha subunit and shared signaling dimers, define its distinct mechanistic, functional, and therapeutic profile[5][1][2][3].

Other names

IL-15R complexIL-15Rα/IL-2/15Rβ/γc complexIL-15 receptor trimerInterleukin-15 receptor alpha chain (IL-15Rα, when referring specifically to the alpha subunit)Common gamma chain receptor (for the γc subunit)

Agonism of IL-15R to enhance NK and T cell activation Antagonism/blockade of IL-15R to suppress immune activation Induction of JAK/STAT pathway signaling by IL-15