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

Int J Cancer. 1999 May 5;81(3):387-94. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm*
  • Carcinoma, Squamous Cell / immunology
  • Cell Line
  • Epitopes, T-Lymphocyte*
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Head and Neck Neoplasms / immunology
  • Humans
  • Neoplasm Proteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A24 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins