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

Interleukin-15 receptor subunit alpha (IL-15Rα) is a high-affinity receptor component essential for the biological activity of IL-15. It primarily functions through a mechanism called trans-presentation, where it binds IL-15 on the surface of antigen-presenting cells and presents it to the IL-2/IL-15 receptor beta-gamma complex on neighboring NK cells or CD8+ T cells (UniProt P43681). This interaction is critical for the development, survival, and activation of these effector immune cells, which are vital for anti-tumor and anti-viral immunity. In the drug nogapendekin alfa inbakicept (Anktiva), a recombinant sushi domain of IL-15Rα is used to create a stable IL-15 superagonist complex. This complex mimics natural trans-presentation to enhance the potency and half-life of IL-15 signaling, selectively stimulating cytotoxic lymphocytes while avoiding the activation of immunosuppressive regulatory T cells (FDA, 2024). Consequently, IL-15Rα serves as both a structural component of modern immunotherapy and a key regulator of the immune response in various cancers and infectious diseases.

Other names

IL15RACD215Interleukin-15 receptor alpha chainIL-15R-alpha

Nogapendekin alfa inbakicept is an IL-15 superagonist complex consisting of an IL-15 mutant (N72D) bound to the sushi domain of the IL-15 receptor alpha (IL-15Rα) subunit fused to an IgG1 Fc. This complex mimics the natural trans-presentation of IL-15 by IL-15Rα to the dimeric IL-2/IL-15 receptor beta-gamma (CD122/CD132) on NK cells and CD8+ T cells, leading to their proliferation and activation without stimulating regulatory T cells (FDA, 2024; Chamie et al., 2022).