Peptide analogues of a subdominant epitope expressed in EBV-associated tumors: Synthesis and immunological activity

H-Cys-Leu-Gly-Gly-Leu-Leu-Thr-Met-Val-OH (CLG) peptide is an EBV subdominan t epitope that represents the target of HLA-A2 restricted CTL responses. Th e CLG peptide has low affinity for HLA-A2 and does not produce stable compl exes, both factors that determine weak CTL responses. In contrast, the [Tyr (1), Ala(3)] CLG (YLA) analogue showed high affinity for HLA-A2 molecules a nd efficiently stimulated CLG-specific CTL precursors. Nevertheless, this m odified epitope showed low enzymatic stability. To further improve the immu notherapeutical potential of this "improved epitope", we have synthesized a nd tested YLA analogues containing different modifications next to the scis sile peptide bond. Among the analogues we found three peptides, with higher enzymatic resistance, that efficiently stimulate CTL responses. These pept ides may be used for EBV-specific immunotherapies.