A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3

Eur J Immunol. 1994 Dec;24(12):3038-43. doi: 10.1002/eji.1830241218.

Abstract

The human MAGE-3 gene is expressed in many tumors of several histological types but it is silent in normal tissues, with the exception of testis. Antigens encoded by MAGE-3 may, therefore, be useful targets for specific anti-tumor immunization of cancer patients. We reported previously that MAGE-3 codes for an antigenic peptide recognized on a melanoma cell line by autologous cytolytic T lymphocytes (CTL) restricted by HLA-A1. Here we report that the MAGE-3 gene also codes for another antigenic peptide that is recognized by CTL restricted by HLA-A2. MAGE-3 peptides bearing consensus anchor residues for HLA-A2 were synthesized and tested for binding. T lymphocytes from normal individuals were stimulated with autologous irradiated lymphoblasts pulsed with each of three peptides that showed strong binding to HLA-A2. Peptide FLWGPRALV was able to induce CTL. We obtained CTL clones that recognized not only HLA-A2 cells pulsed with this peptide but also HLA-A2 tumor cell lines expressing the MAGE-3 gene. The proportion of melanoma tumors expressing this antigen should be approximately 32% in Caucasian populations, since 49% of individuals carry the HLA-A2 allele and 65% of melanomas express MAGE-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunity, Cellular
  • In Vitro Techniques
  • Melanoma / immunology
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Peptides / chemistry
  • Peptides / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Cytokines
  • HLA-A2 Antigen
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Peptides