A tyrosinase nonapeptide presented by HLA-B44 is recognized on a human melanoma by autologous cytolytic T lymphocytes.
The human tyrosinase gene has been reported previously to code for two distinct antigens recognized on HLA-A2 melanoma cells by autologous cytolytic T lymphocytes (CTL). By stimulating lymphocytes of melanoma patient MZ2 with a subclone of the tumor cell line of this patient, we obtained a CTL clone that lysed this subclone but did not lyse other subclones of the same melanoma cell line. The sensitive melanoma subclone was found to express a much higher level of tyrosinase than the others, suggesting that the antigen recognized by the CTL might be encoded by tyrosinase. Transfection of a tyrosinase cDNA demonstrated that the CTL clone indeed recognized a tyrosinase product presented by HLA-B*4403. The relevant antigenic peptide corresponds to residues 192-200 of the tyrosinase protein. Lymphoblastoid cells of the B*4402 subtype were not recognized by the CTL following incubation with the peptide. Nevertheless, by stimulating in vitro lymphocytes of a healthy HLA-B*4402 donor with autologous adherent cells pulsed with the same peptide, we obtained a CTL clone which recognized tumor cells expressing tyrosinase and HLA-B*4402. As HLA-B44 is expressed in 24% of Caucasians, the tyrosinase-B44 antigen may constitute a useful target for specific immunotherapy of melanoma.
Brichard
V G
VG
Ludwig Institute for Cancer Research, Brussels, Belgium.
Herman
J
J
Van Pel
A
A
Wildmann
C
C
Gaugler
B
B
Wölfel
T
T
Boon
T
T
Lethé
B
B
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D059948:HLA-B44 Antigen; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000276:immunology*; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D009842:Oligopeptides; D014442:Monophenol Monooxygenase