Design of dimeric peptides obtained from a subdominant Epstein-Barr virus LMP2-derived epitope

The latent membrane protein 2 (LMP2) is expressed in EBV-associated tumours . LMP2 is a target of HLA-A2 restricted EBV-specific CTL responses and cons equently it may represent a good target for specific CTL-based immunotherap ies. However, the efficacy of such therapy is limited by the poor immunogen icity of the protein that induces weak cytotoxic T lymphocyte (CTL) respons es directed against the CLGGLLTMV (CLG) epitope. Indeed, the CLG peptide pr esents low affinity for HLA-A2 and does not produce stable complexes. There fore we synthesized and tested CLG-dimeric analogues with the purpose of ch aracterizing new compounds with the capacity to bind HLA-A2 molecules. By t hese studies we have identified a few peptides which, compared to the natur al epitope, showed higher affinity for HLA-A2 molecules and superior capaci ty to form a complex. These dimeric peptides may have the potential to indu ce efficient CTL responses directed to the natural epitope. (C) 2000 Editio ns scientifiques et medicales Elsevier SAS.