A newly identified MAGE-3-derived epitope recognized by HLA-A24-restricted cytotoxic T lymphocytes

✍ Scribed by Masatake Oiso; Masao Eura; Fumihiro Katsura; Masafumi Takiguchi; Yuji Sobao; Keisuke Masuyama; Manabu Nakashima; Kyogo Itoh; Takeru Ishikawa

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 123 KB
• Volume: 81
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990505)81:3<387::aid-ijc12>3.0.co;2-z

✦ Synopsis

Five MAGE-3-derived peptides carrying an HLA-A24binding motif were synthesized. Binding capacity of these peptides was analyzed by an HLA-class-I stabilization assay. Two of the 5 peptides bound to HLA-A*2402 molecule with high affinity, and 3 peptides with low affinity. Peripheral-blood mononuclear cells (PBMC) depleted of CD4 ؉ T cells were stimulated with the peptides to determine whether these peptides would induce cytotoxic T lymphocytes (CTL) from PBMCs obtained from 7 healthy HLA-A*2402 ؉ donors. Peptide M3-p97 (TFPDLESEF; corresponding to amino-acid residues 97-105 of MAGE-3), with high binding capacity to the HLA-A*2402 molecule, elicited the peptide-specific and HLA-A24-restricted CD8 ؉ CTL lines in 2 of the 7 donors, while none of the 4 other peptides induced CTL specific for the corresponding peptide in any of the donors. CTL lines induced by stimulation with peptide M3-p97 exhibited cytolytic activities against HLA-A*2402 transfectant cell lines (C1R-A*2402) in the presence of peptide M3-p97, but not in unloaded or irrelevant peptide-pulsed C1R-A*2402 cells. The CTL lines and a cloned CD8 ؉ CTL isolated from one of the bulk populations by limiting dilution could lyse MAGE-3 ؉ /HLA-A*2402 ؉ squamous-cell-carcinoma(SCC) lines but neither MAGE-3 ؊ /HLA-A*2402 ؉ nor MAGE-3 ؉ /HLA-A*2402 ؊ SCC lines, indicating that M3-p97 can be naturally processed and presented on the tumor-cell surface in association with HLA-A*2402 molecules. Combined with the 4 currently reported CTL epitopes derived from MAGE-3 and presented by HLA-A1, HLA-A2, HLA-A24 or HLA-B44, identification of this CTL epitope presented by the HLA-A*2402 molecule will extend the application of MAGE-3-derived peptides for immunotherapy for cancer patients.