Interleukin-15 receptor alpha (IL15RA) is a key component of the heterotrimeric IL-15 receptor complex, which also includes IL-2Rβ and the common gamma chain (γc). As a high-affinity binding subunit, IL15RA specifically interacts with IL-15. a pleiotropic cytokine critical for the development, survival, and activation of immune cells, particularly natural killer (NK) cells and memory CD8+ T cells. Structurally, IL15RA contains extracellular cytokine-binding domains, a transmembrane region, and a short cytoplasmic tail that facilitates signal transduction through JAK-STAT pathways.
Antibodies targeting IL15RA have emerged as valuable tools for modulating IL-15 signaling in both research and therapeutic contexts. In research, anti-IL15RA antibodies are used to block IL-15/IL15RA interactions, enabling studies on immune regulation, autoimmune diseases, and cancer immunology. Therapeutically, antagonistic anti-IL15RA antibodies are explored for treating autoimmune disorders like rheumatoid arthritis or inflammatory bowel disease by suppressing pathological immune activation. Conversely, agonist antibodies that mimic IL-15 trans-presentation (a unique mechanism where IL15RA presents IL-15 to neighboring cells) are being investigated to boost anti-tumor immunity. Challenges include balancing efficacy with potential off-target effects, as IL-15 signaling supports both pro-inflammatory and homeostatic immune functions. Recent preclinical studies highlight the potential of IL15RA-targeting bispecific antibodies and antibody-drug conjugates in precision immunotherapy. Overall, IL15RA antibodies represent a versatile strategy for immune modulation, with ongoing clinical trials evaluating their safety and therapeutic potential.