A newly identified MAGE-3-derived epitope recognized by HLA-A24-restricted cytotoxic T lymphocytes.
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.
Oiso
M
M
Department of Otolaryngology, Kumamoto University School of Medicine, Honjo, Japan.
Eura
M
M
Katsura
F
F
Takiguchi
M
M
Sobao
Y
Y
Masuyama
K
K
Nakashima
M
M
Itoh
K
K
Ishikawa
T
T
D000951:Antigens, Neoplasm; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006258:Head and Neck Neoplasms / Q000276:immunology; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins