Comprehensive Identification of Immune Complex Antigens and Epitopes for Disease Understanding and Next-generation Therapeutics

Immune complexes (ICs), formed through antigen–antibody interactions, are direct products of immune responses. They are involved in the pathogenesis of autoimmune diseases, infections, and cancers. Conventional IC studies have largely focused on their quantity and tissue deposition, whereas the antigenic components within ICs remain insufficiently characterized. Immune complexome analysis, a method that combines protein A/G-based IC isolation with nanoscale LC-MS/MS, enables comprehensive identification of the antigens present in circulating ICs. Using this approach, I identified disease-associated IC antigens in a variety of diseases. These findings suggest that IC antigens may reflect disease-specific immune responses and provide valuable information for biomarker discovery, disease characterization, and therapeutic target identification. Furthermore, I am developing an epitope-mapping strategy based on cross-linking mass spectrometry to investigate antigen–antibody interaction sites within ICs. This approach is expected to provide deeper insights into disease-associated immune responses and facilitate the development of antibody therapeutics, vaccines, and precision medicine.