Synthetic approaches to T-cell epitope determination have recently bee
n 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 th
ese different strategies opens new possibilities for basic, as well as
for applied, immunology. The outlines of the strategies for determina
tion 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 w
ith random synthetic peptide libraries allow comprehensive surveys of
the sequence requirements for peptide selection by MHC molecules and f
or induction of T-cell responses. Synthetic T-cell epitopes can be det
ermined 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.