Class II major histocompatibility complex (MHC-II) antigens (Ags) are integral membrane glycoproteins that have the unique capacity to bind prepro-cessed peptides, and present them to the immune system. These peptides are derived through a complex series of intracellular processing events that diverge among the plentitude of Ags presented in the context of MHC-II. The trimeric complex, consisting of peptide and class II α- and β-chains, is recognized by epitope specific CD4⁺T-cells. This fine specificity exhibited by the T-cell receptor is fundamental to the induction of tolerance and pathogen clearance. Therefore, delineating the mechanisms by which certain epitopes are generated and presented to CD4⁺T-cells may be useful in the development of immu-notherapies for solid tumors and autoimmune diseases, and more efficacious vaccines.