Interleukin-2 receptor subunit beta–cytokine receptor common gamma chain heterodimer (IL-2Rβγ) (IL-2Rβγ)

The Interleukin-2 receptor subunit beta–cytokine receptor common gamma chain heterodimer is a signaling complex composed of the IL-2Rβ (CD122) and γc (CD132) subunits (UniProt P14784, P31785). This heterodimer serves as the intermediate-affinity receptor for interleukin-2 (IL-2) and is the essential signaling component for interleukin-15 (IL-15) (PubMed: 22391154). It is constitutively expressed on memory CD8+ T cells and natural killer (NK) cells, whereas the high-affinity trimeric receptor (which includes IL-2Rα/CD25) is primarily found on regulatory T cells (Tregs) (PubMed: 29924973). Upon ligand binding, the heterodimer recruits Janus kinases JAK1 and JAK3 to initiate the STAT5, PI3K/Akt, and MAPK signaling pathways, which are critical for lymphocyte survival and effector function (PubMed: 31515344). In oncology, this complex is a major target for biased IL-2 agonists, such as bempegaldesleukin, designed to selectively activate CD8+ T and NK cells while avoiding the activation of immunosuppressive Tregs (PubMed: 31515344). Therapeutic modulation of this receptor complex is also explored in autoimmune diseases and chronic infections to fine-tune the balance of the immune response.

Other names

CD122/CD132 complexIntermediate-affinity IL-2 receptorIL-2Rβ/γcIL-15 receptor signaling complexIL-2Rβγ

Agonism of the IL-2/IL-15 signaling pathway via JAK/STAT activation; selective stimulation of effector T cells and NK cells.