Multiple specificities in the repertoire of a melanoma patient's cytolytic T lymphocytes directed against tumor antigen MAGE-1.A1.
Peptide MAGE-1.A1 is a nonamer derived from protein MAGE-1 that can associate with the HLA-A1 molecule. It was shown previously to be recognized by an antitumor cytolytic T lymphocyte (CTL) clone derived from the blood of melanoma patient MZ2. We derived two other anti-MAGE-1.A1 CTL clones from different blood samples of the same patient and compared the fine specificity of recognition of the three CTL by testing them on variant MAGE-1.A1 peptides incorporating different amino acid substitutions. The epitopes recognized by the CTL proved to be different. While modifications of residues at positions 5, 6, or 7 in the antigenic peptide affected recognition by the three CTL, each of the modifications of residues at positions 1, 4, or 8 affected recognition by one CTL only. The sequences of both the alpha and beta chains of the T cell antigen receptor of the three CTL were completely different. The results indicate a long-lasting diversity in terms of fine specificity and of T cell antigen receptor structure in the repertoire of antitumor CTL derived from the blood of a melanoma patient and directed against a defined tumor antigen.
Romero
P
P
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Pannetier
C
C
Herman
J
J
Jongeneel
C V
CV
Cerottini
J C
JC
Coulie
P G
PG
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D002999:Clone Cells; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009842:Oligopeptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta