A MAGE-1 antigenic peptide recognized by human cytolytic T lymphocytes on HLA-A2 tumor cells.
"Cancer-germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in normal tissues. They encode shared tumor-specific antigens that have been used in therapeutic vaccination trials of cancer patients. It was previously demonstrated that MAGE-1 peptide KVLEYVIKV was presented by HLA-A 0201 molecules on the surface of a human breast carcinoma cell line, but no human specific CTL had been isolated so far. Here, we have used HLA-A2/MAGE-1 fluorescent multimers to isolate from blood cells three human CTL clones that recognized the MAGE-1 peptide. These clones killed efficiently HLA-A2 tumor cells expressing MAGE-1, whether or not they were treated with IFN-gamma, suggesting that the MAGE-1 antigen is processed efficiently by both the standard proteasome and the immunoproteasome. These results indicate that the MAGE-1.A2 peptide can be used for antitumoral vaccination.
Ottaviani
Sabrina
S
Ludwig Institute for Cancer Research and Cellular Genetics Unit, University of Louvain, 74 avenue Hippocrate, UCL 74.59, 1200 Brussels, Belgium.
Zhang
Yi
Y
Boon
Thierry
T
van der Bruggen
Pierre
P
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; C506530:MAGE-A1 protein (278-286), human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D046988:Proteasome Endopeptidase Complex