A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3.
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.
van der Bruggen
P
P
Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium.
Bastin
J
J
Gajewski
T
T
Coulie
P G
PG
Boël
P
P
De Smet
C
C
Traversari
C
C
Townsend
A
A
Boon
T
T
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008545:Melanoma / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D016207:Cytokines; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010455:Peptides