MHC class I molecules bind short peptides, 8-10 amino acids long, derived from proteins expressed inside the cells, and present them at the cell surface for surveillance by cytotoxic T lymphocytes (CTL). Bound peptides form an integral part with MHC molecules and, together with β2-microglobulin, induce stable trimolecular complexes. In the last few years we have studied MHC/peptide association and the role of specific residues in T cell activation. The ultimate purpose of our research is the design of new peptide epitodes, derived from viral and tumoral antigens, with high immunogenicity that can be used in new protocols of immunotherapy.