Interleukin-2 receptor high-affinity trimeric complex (Mouse) (IL-2R)

The mouse high-affinity interleukin-2 (IL-2) receptor is a heterotrimeric protein complex composed of the alpha (CD25), beta (CD122), and common gamma (CD132) subunits (UniProt: P01590, P16297, P34902). It is primarily expressed on regulatory T cells (Tregs) and activated effector T cells, where it binds the cytokine IL-2 with exceptionally high affinity (Kd ~10^-11 M) to initiate critical survival and proliferation signals (PubMed: 12401408). Upon ligand binding, the receptor triggers intracellular signaling through the JAK/STAT (specifically JAK1/JAK3 and STAT5), PI3K/Akt, and MAPK pathways, which are essential for maintaining immune homeostasis and driving adaptive immune responses (PubMed: 16484495). In mouse models, genetic deficiency of any receptor subunit leads to severe, early-onset autoimmune and lymphoproliferative diseases, underscoring its role in immune tolerance (PubMed: 11859342). The receptor is a key target in preclinical research, where low-dose IL-2 is used to expand Tregs for treating inflammatory conditions, while monoclonal antibodies like PC61 are employed to deplete CD25+ cells in cancer or transplantation studies (PubMed: 2630524). Understanding the structural and functional nuances of the mouse IL-2 receptor trimer is vital for the development and validation of novel immunotherapies before they transition to human clinical trials.

Other names

CD25/CD122/CD132 complexIL-2RαβγHigh-affinity IL-2 receptorTrimeric IL-2 receptorInterleukin-2 receptor alpha/beta/gamma complex

The mechanism of action for drugs targeting the mouse high-affinity IL-2 receptor involves the modulation of Interleukin-2 (IL-2) signaling pathways. Antagonistic monoclonal antibodies, such as PC61, bind to the CD25 subunit to competitively inhibit IL-2 binding or induce the depletion of activated T cells and regulatory T cells (Tregs) via antibody-dependent cellular cytotoxicity (ADCC) (PubMed: 2630524). Conversely, agonistic approaches like low-dose IL-2 or IL-2/anti-IL-2 cytokine complexes (e.g., JES6-1) selectively activate the high-affinity trimeric receptor to expand the Treg population, thereby restoring immune tolerance in autoimmune and inflammatory models (PubMed: 16484495).