T-cell epitope determination.

Synthetic approaches to T-cell epitope determination have recently been developed that complement the search for natural T-cell epitopes and the investigation of the preferences of the different MHC alleles for particular motifs in cognate peptide sequences. The combination of these different strategies opens new possibilities for basic, as well as for applied, immunology. The outlines of the strategies for determination of natural T-cell epitopes are well established. These strategies have contributed substantially to our understanding of the nature of T-cell epitopes and of many diseases. Positional scanning approaches with random synthetic peptide libraries allow comprehensive surveys of the sequence requirements for peptide selection by MHC molecules and for induction of T-cell responses. Synthetic T-cell epitopes can be determined independently of the knowledge of the natural T-cell antigen. This opens new perspectives for the development of synthetic vaccines, TCR antagonists and MHC blockers.