Interleukin-15 receptor subunit beta and cytokine receptor common subunit gamma complex (IL-15Rβγ) (IL-15Rβγ)

The Interleukin-15 receptor subunit beta and cytokine receptor common subunit gamma complex (IL-15Rβγ) is a heterodimeric signaling unit essential for the development and maintenance of the innate and adaptive immune systems. Composed of the IL-15 receptor subunit beta (CD122) and the common gamma chain (CD132), this complex is primarily expressed on memory CD8+ T cells and Natural Killer (NK) cells. Unlike the high-affinity heterotrimeric receptor that includes the alpha subunit (IL-15Rα), the βγ complex possesses intermediate affinity and is the primary transducer of signals through the JAK/STAT pathway, specifically activating JAK1 and JAK3 to trigger STAT5-mediated gene transcription. In oncology, the IL-15Rβγ complex is a high-priority therapeutic target for superagonists and biased ligands designed to stimulate anti-tumor immunity. These drugs aim to mimic the natural trans-presentation of IL-15, promoting the expansion of cytotoxic lymphocytes without the severe toxicities or regulatory T cell (Treg) activation associated with high-dose Interleukin-2 therapy. Clinical applications include the treatment of non-muscle invasive bladder cancer and various solid tumors, where the goal is to enhance immune surveillance and overcome the immunosuppressive tumor microenvironment.

Other names

IL-15 receptor beta/gamma complexCD122/CD132 complexIntermediate-affinity IL-15 receptorIL-2/15Rβγc complexInterleukin-15 receptor subunit beta and common cytokine receptor gamma chain

IL-15 receptor agonism, JAK/STAT pathway activation, Trans-presentation mimicry, Selective CD122/CD132 activation