Interleukin-15 receptor heterotrimer (IL-15R)

The Interleukin-15 receptor heterotrimer is a high-affinity signaling complex essential for the development, survival, and activation of natural killer (NK) cells and memory CD8+ T lymphocytes (UniProt, Wikipedia). It is composed of three distinct subunits: the ligand-specific Interleukin-15 receptor subunit alpha (IL-15RA), the shared Interleukin-2 receptor subunit beta (CD122), and the cytokine receptor common subunit gamma (CD132) (NIH, PubMed). A defining feature of this receptor is the "trans-presentation" mechanism, where IL-15 is presented by IL-15RA on the surface of an antigen-presenting cell to the beta-gamma signaling dimer on an adjacent effector cell (Nature, NIH). This interaction triggers downstream signaling through the JAK/STAT, PI3K/Akt, and MAPK pathways, promoting immune cell proliferation and effector function (PubMed, Wikipedia). In therapeutic contexts, IL-15 receptor agonists are utilized in oncology to stimulate anti-tumor immunity, offering a more selective alternative to IL-2 by avoiding the expansion of regulatory T cells (NCI, ClinicalTrials.gov). Conversely, antagonists targeting the receptor complex are investigated for treating autoimmune and inflammatory diseases, such as celiac disease and rheumatoid arthritis, where dysregulated IL-15 signaling contributes to chronic inflammation and tissue damage (NIH, PubMed).

Other names

IL-15 receptor complexIL-15RαβγCD122/CD132/IL-15RA complexInterleukin-15 receptor subunit alpha/beta/gamma complex

Agonists bind to the IL-2/IL-15 receptor beta and common gamma subunits to activate JAK/STAT signaling, while antagonists block these subunits to inhibit pro-inflammatory responses.