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

Interleukin-15 receptor subunit alpha (IL-15RA) is a high-affinity transmembrane protein essential for the biological activity of the cytokine IL-15. It is uniquely characterized by its trans-presentation mechanism, where it binds IL-15 and presents it on the cell surface to neighboring effector cells, such as natural killer (NK) cells and CD8+ T cells, which express the IL-2/IL-15 receptor beta (CD122) and common gamma (CD132) chains (UniProt P43080; Waldmann, T. A., 2006, J Clin Immunol). In the field of adoptive cell therapy, NK cells are often engineered to co-express IL-15 and IL-15RA to create a membrane-bound signaling complex. This engineering strategy provides a continuous survival signal through autocrine and paracrine loops, significantly enhancing the anti-tumor potency and persistence of CAR-NK cells in treating malignancies (Liu, E., et al., 2020, NEJM). Clinically, IL-15RA is utilized via IL-15/IL-15RA complexes like N-803, which are designed to mimic natural trans-presentation and stimulate robust immune responses against cancer (Romee, R., et al., 2016, Sci Transl Med).

Other names

CD215IL-15 receptor alpha chainIL15RAInterleukin-15 receptor subunit alpha

IL-15RA binds IL-15 with high affinity and trans-presents it to the IL-2/IL-15 receptor beta (CD122) and common gamma (CD132) chains on effector cells, triggering the JAK/STAT signaling pathway to promote immune cell survival and expansion (UniProt P43080; Waldmann, T. A., 2006, J Clin Immunol).