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

J Immunol. 2003 Jul 1;171(1):219-25. doi: 10.4049/jimmunol.171.1.219.

Abstract

"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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation* / genetics
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cell Line, Transformed
  • Cell Separation
  • Cells, Cultured
  • Clone Cells
  • HLA-DR1 Antigen / metabolism*
  • Humans
  • Injections, Intradermal
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / prevention & control
  • Melanoma-Specific Antigens
  • Molecular Sequence Data
  • Neoplasm Proteins / administration & dosage
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Proteins / metabolism
  • Tumor Cells, Cultured
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-DR1 Antigen
  • MAGEA1 protein, human
  • MAGEA10 protein, human
  • MAGEA3 protein, human
  • MAGEA4 protein, human
  • MAGEL2 protein, human
  • Mageb1 protein, mouse
  • Mageb3 protein, mouse
  • Magel2 protein, mouse
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Peptide Fragments
  • Proteins
  • Vaccines, Synthetic