Interleukin-15 receptor subunit alpha (IL-15RA) (IL-15RA)

The Interleukin-15 receptor subunit alpha (IL-15RA) is a high-affinity transmembrane protein that is essential for the biological activity of the cytokine Interleukin-15 (IL-15) (UniProt: P43681). It functions primarily through a unique mechanism called trans-presentation, where IL-15RA on the surface of dendritic cells or macrophages presents IL-15 to the IL-2/IL-15 receptor beta (CD122) and common gamma (CD132) chains on natural killer (NK) cells and CD8+ T cells (Waldmann, 2015, Nature Reviews Immunology). This interaction is crucial for the development, survival, and activation of these cytotoxic immune cells, making the IL-15/IL-15RA complex a potent target for cancer immunotherapy (PubMed: 17591855). Therapeutic strategies often involve superagonists like Nogapendekin alfa inbakicept (Anktiva), which consist of an IL-15 mutant bound to the sushi domain of IL-15RA to mimic and enhance natural signaling (FDA.gov, 2024). These agents are designed to stimulate anti-tumor immunity with improved stability and reduced systemic toxicity compared to recombinant IL-15 monomers (PubMed: 23847182). Conversely, the IL-15 signaling pathway is implicated in the pathogenesis of various autoimmune and inflammatory diseases, such as rheumatoid arthritis and celiac disease, where overactive T-cell responses drive tissue damage (PubMed: 30108615). Consequently, both agonistic complexes for oncology and antagonistic approaches for autoimmunity represent significant areas of clinical development.

Other names

CD215IL-15R-alphaIL15RAInterleukin-15 receptor alphaIL-15 signaling complex

Agonism of the IL-15 signaling pathway via trans-presentation mimicry to stimulate NK and CD8+ T cell proliferation; Antagonism of the IL-15/IL-15RA interaction to inhibit pro-inflammatory signaling.