A MAGE-3 peptide presented by HLA-DR1 to CD4+ T cells that were isolated from a melanoma patient vaccinated with a MAGE-3 protein.
"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 Ags, which have been used in therapeutic vaccination trials of cancer patients. MAGE-3 is expressed in 74% of metastatic melanoma and in 50% of carcinomas of esophagus, head and neck, bladder, and lung. We report here the identification of a new MAGE-3 peptide, which is recognized by three different CD4(+) T cell clones isolated from a melanoma patient vaccinated with a MAGE-3 protein. These clones, which express different TCRs, recognize an HLA-DR1 peptide ACYEFLWGPRALVETS, which corresponds to the MAGE-3(267-282) and the MAGE-12(267-282) protein sequences. One of the T cell clones, which expresses LFA-1 at a high level, lysed tumor cells expressing DR1 and MAGE-3. Another of these DR1-restricted CD4(+) clones recognized not only the MAGE-3/12 peptide but also homologous peptides encoded by genes MAGE-1, 2, 4, 6, 10, and 11.
Zhang
Yi
Y
Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, Brussels, Belgium.
Chaux
Pascal
P
Stroobant
Vincent
V
Eggermont
Alexander M M
AM
Corthals
Jurgen
J
Maillère
Bernard
B
Thielemans
Kris
K
Marchand
Marie
M
Boon
Thierry
T
Van Der Bruggen
Pierre
P
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D002469:Cell Separation; D002478:Cells, Cultured; D002999:Clone Cells; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D006801:Humans; D007271:Injections, Intradermal; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015798:HLA-DR1 Antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011506:Proteins; D014614:Vaccines, Synthetic; C072011:MAGEA1 protein, human; C121012:MAGEA10 protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C510822:MAGEL2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D064267:Intrinsically Disordered Proteins; C489518:Mageb1 protein, mouse; C489519:Mageb3 protein, mouse; C403091:Magel2 protein, mouse