T cells recognize a broad variety of antigens, including peptides, lipids and non-peptidic phosphorylated metabolites. Clarification of the rules rendering non-peptidic molecules immunogenic is essential to understand and to influence the reactions of the immune system to this class of substances in health and disease. Molecular mechanisms governing the immunogenicity of non-peptidic ligands such as their cell internalization, trafficking within intracellular organelles, association with dedicated antigen-presenting molecules, induction of central and peripheral tolerance, and finally their...