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 consequently it may represent a good target for specific CTL-based immunotherapies. However, the efficacy of such therapy is limited by the poor immunogenicity of the protein that induces weak cytotoxic T lymphocyte (CTL) responses directed against the CLGGLLTMV (CLG) epitope. Indeed, the CLG peptide presents low affinity for HLA-A2 and does not produce stable complexes. Therefore we synthesized and tested CLG-dimeric analogues with the purpose of characterizing new compounds with the capacity to bind HLA-A2 molecules. By these studies we have identified a few peptides which, compared to the natural epitope, showed higher affinity for HLA-A2 molecules and superior capacity to form a complex. These dimeric peptides may have the potential to induce efficient CTL responses directed to the natural epitope.
Marastoni
M
M
Department of Pharmaceutical Sciences, Via Fossato di Mortara 15-19 and Biotechnology Centre, Via Fossato di Mortara 64, University of Ferrara, 44100, Ferrara, Italy. grm@dns.unife.it
Bazzaro
M
M
Gavioli
R
R
Micheletti
F
F
Traniello
S
S
Tomatis
R
R
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001671:Biochemistry / Q000379:methods; D002460:Cell Line; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry*; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D013329:Structure-Activity Relationship; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*
D000596:Amino Acids; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides; D014763:Viral Matrix Proteins; C023820:11-aminoundecanoic acid