Interleukin-2–Interleukin-2 receptor alpha protein–protein interaction (IL-2–IL-2Rα PPI)

The Interleukin-2 (IL-2) and Interleukin-2 receptor alpha (IL-2Rα, or CD25) protein-protein interaction (PPI) is a fundamental regulatory event in the adaptive immune system. IL-2 is a cytokine primarily produced by activated T cells that drives the expansion and survival of various lymphocyte subsets. The IL-2 receptor (IL-2R) is composed of three subunits: alpha (CD25), beta (CD122), and gamma (CD132). While the beta and gamma subunits form an intermediate-affinity receptor, the addition of the alpha subunit creates a high-affinity complex that allows cells to respond to very low concentrations of IL-2. This interaction is particularly vital for the function of regulatory T cells (Tregs) and the rapid proliferation of effector T cells during an immune response. Clinically, this PPI is targeted by monoclonal antibodies like basiliximab to prevent acute organ rejection by blocking IL-2-mediated T-cell activation. Additionally, engineered IL-2 variants (IL-2 mutes) are being developed to selectively target or avoid this interaction to tune the immune response for cancer immunotherapy or autoimmune treatment.

Other names

IL-2/CD25 interactionInterleukin-2/Interleukin-2 receptor subunit alpha interactionIL-2/IL-2RA PPITac antigen interaction

Competitive inhibition of IL-2 binding to the CD25 (alpha) subunit of the IL-2 receptor, preventing the assembly of the high-affinity heterotrimeric receptor complex and subsequent downstream signaling via the JAK-STAT pathway.