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

The Interleukin-15 receptor heterotrimer is a high-affinity signaling complex composed of three distinct subunits: IL-15Rα (CD215), IL-2/IL-15Rβ (CD122), and the common gamma chain (γc, CD132) (UniProt P43681, P14784, P31785). While IL-15Rα primarily functions to capture and "trans-present" IL-15 to neighboring cells, the β and γ subunits are responsible for initiating intracellular signaling via the JAK/STAT pathway (PMID: 16551251). This receptor complex plays a critical role in the development, survival, and activation of natural killer (NK) cells and memory CD8+ T cells, making it a vital component of the adaptive and innate immune systems. In oncology, the receptor is targeted by IL-15 agonists and superagonists to enhance anti-tumor immunity by expanding effector cell populations without the significant regulatory T-cell (Treg) stimulation associated with IL-2 (PMID: 28213345). Conversely, dysregulation of IL-15 signaling is implicated in various autoimmune and inflammatory conditions, where the receptor may be targeted for inhibition. Therapeutic strategies currently focus on leveraging the high-affinity heterotrimer to treat solid tumors and hematological malignancies, often in combination with checkpoint inhibitors or cell therapies (FDA.gov).

Other names

IL-15 receptor complexIL-15Rα/β/γCD215/CD122/CD132 complexHigh-affinity IL-15 receptor

Agonism of the heterotrimeric receptor complex leads to the activation of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3), subsequently triggering the phosphorylation and nuclear translocation of STAT3 and STAT5 to promote the survival and proliferation of CD8+ T cells and natural killer (NK) cells (UniProt P43681; PMID: 16551251).