Experimental discovery of T-cell epitopes: combining the best of classical and contemporary approaches

T cells specifically recognize antigens as peptide epitope-MHC complexes on the surface of target cells. The inherent complexities of antigen processing and presentation, the polygenic and polymorphic nature of MHC and the technical hurdles in working with T cells have made epitope discovery challenging. Here, we review significant experimental advances in recent years. These include new and sensitive assays and the availability of human cells and high numbers of synthetic peptides for screening, which have allowed for the first time comprehensive analysis of antigens and whole virus genomes. Such studies have provided important insights into the immunobiology of a number of diseases. The newly gathered detailed information on T-cell epitopes will aid vaccine design and immunological monitoring in clinical trials.