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

• Published in: International journal of cancer 1999-05, Vol.81 (3), p.387-394
• Main Authors: Oiso, Masatake, Eura, Masao, Katsura, Fumihiro, Takiguchi, Masafumi, Sobao, Yuji, Masuyama, Keisuke, Nakashima, Manabu, Itoh, Kyogo, Ishikawa, Takeru
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm; Biological and medical sciences; Carcinoma, Squamous Cell - immunology; Cell Line; Epitopes, T-Lymphocyte; Head and Neck Neoplasms - immunology; HLA-A Antigens - immunology; HLA-A24 Antigen; Host-tumor relations. Immunology. Biological markers; Humans; Medical sciences; Neoplasm Proteins - immunology; T-Lymphocytes, Cytotoxic - immunology; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990505)81:3<387::AID-IJC12>3.0.CO;2-Z

Five MAGE‐3‐derived peptides carrying an HLA‐A24‐binding 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. Int. J. Cancer 81:387–394, 1999. © 1999 Wiley‐Liss, Inc.