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A newly identified MAGE‐3 ‐derived epitope recognized by HLA‐A24‐restricted cytotoxic T lymphocytes
Author(s) -
Oiso Masatake,
Eura Masao,
Katsura Fumihiro,
Takiguchi Masafumi,
Sobao Yuji,
Masuyama Keisuke,
Nakashima Manabu,
Itoh Kyogo,
Ishikawa Takeru
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990505)81:3<387::aid-ijc12>3.0.co;2-z
Subject(s) - ctl* , cytotoxic t cell , cd8 , epitope , peptide , human leukocyte antigen , peripheral blood mononuclear cell , microbiology and biotechnology , mhc class i , biology , cytolysis , virology , antigen , chemistry , immunology , biochemistry , in vitro
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.