Intermediate-affinity interleukin-2 receptor beta-gamma complex (IL-2Rβγ)

The intermediate-affinity interleukin-2 receptor (IL-2Rβγ) is a heterodimeric signaling complex consisting of the IL-2 receptor beta subunit (CD122) and the common gamma chain (CD132) (Source: UniProt P14784, P31785). It is predominantly expressed on natural killer (NK) cells and resting or memory CD8+ T cells, where it mediates immune activation and proliferation upon binding to interleukin-2 (IL-2) (Source: PMID: 16670703). Unlike the high-affinity trimeric receptor (αβγ) that includes CD25 and is constitutively expressed on immunosuppressive regulatory T cells (Tregs), the βγ complex requires higher concentrations of IL-2 for activation (Source: PMID: 31015319). In the context of cancer immunotherapy, the IL-2Rβγ complex is a high-priority target for "not-alpha" IL-2 variants designed to selectively stimulate anti-tumor effector cells while minimizing the pro-tumorigenic expansion of Tregs (Source: Nektar Therapeutics, Alkermes). Therapeutic strategies include PEGylated IL-2 prodrugs and engineered IL-2 fusion proteins that sterically or mutationally block CD25 binding (Source: PMID: 32335504). Successful engagement of this receptor complex triggers the JAK/STAT5 signaling pathway, enhancing the cytolytic capacity of the immune system against malignancies (Source: StatPearls).

Other names

IL-2RβγCD122/CD132 complexDimeric IL-2 receptorIL-2 receptor subunit beta/gamma complexIntermediate-affinity IL-2 receptor

Selective agonism of the IL-2Rβγ complex to stimulate effector T cells and NK cells while bypassing CD25-mediated Treg activation.