Interleukin-15 receptor beta and common gamma chain complex (IL-15Rβγc complex)

The IL-15Rβγc complex is a cell surface receptor composed of the beta chain (shared with IL-2 receptor: IL-2Rβ, also called CD122) and the common gamma chain (γc, also called CD132) and is a major signaling complex on natural killer (NK) cells and CD8+ T cells. Interleukin-15 (IL-15), a four-helix cytokine structurally related to IL-2, binds to this complex either directly, or via a process called trans-presentation involving the IL-15Rα subunit on antigen-presenting cells. Engagement of the IL-15Rβγc complex activates intracellular signaling pathways such as JAK/STAT and PI3K/AKT, resulting in potent immune stimulation, cell survival, and anti-apoptotic effects. The pathway is the central mediator of IL-15-driven NK and CD8+ T cell proliferation and is exploited in cancer immunotherapy using engineered cytokine agonists such as ALT-803 (IL-15N72D:IL-15RαSu/Fc), which delivers enhanced receptor engagement, improved pharmacokinetics, and potent antitumor activity. Safety profiles are considered favorable compared to related cytokine pathways due to lower risk of regulatory T cell activation and vascular leak.

Other names

IL-2/15Rβγc complexIL-15Rβγc signaling complexCommon cytokine receptor gamma chain complex

Agonist binding: IL-15 binds to IL-15Rβγc leading to JAK1 and JAK3 activation, phosphorylation of STAT3/STAT5/STAT6 transcription factors, PI3K/AKT/mTOR and MAPK signaling; induces proliferation and activation of NK and CD8+ T cells. Trans-presentation: IL-15 bound to IL-15Rα on antigen-presenting cells (monocytes, dendritic cells) is presented to IL-15Rβγc on NK and T cells, leading to their activation. Cytokine receptor engagement: Triggers anti-apoptotic, cell survival, and immune effector functions.