Traditionally, research on the adaptive immune system has focused on protein antigens, but emerging evidence has underscored the essential role of lipid antigens in immune modulation. Lipid antigens are presented by CD1 molecules and activate invariant natural killer T (iNKT) cells and group 1 CD1-restricted T cells, whereby they impact immune responses to pathogens and tumors. Recent advances in mass spectrometry, imaging techniques, and lipidomics have revolutionized the identification and characterization of lipid antigens and enhanced our understanding of their structural diversity and functional significance. These advancements have paved the way for lipid-based vaccines and immunotherapies through the application of nanoparticles and synthetic lipid antigens designed to boost immune responses against cancers and infectious diseases. Lipid trafficking, CD1 molecule interactions, and the immune system's response to lipid antigens are yet to be completely understood, particularly in the context of autoimmunity and microbial infections. In the years to come, continued research efforts are needed to uncover its underlying biological mechanisms and to exploit the full potential of therapies directed against lipid antigens.
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