A new tyrosinase epitope recognized in the HLA-B*4002 context by CTL from melanoma patients.
Melanoma reactive CTL were obtained by stimulating PBL from a melanoma patient in remission since 1994 following adjuvant TIL immunotherapy, with the autologous melanoma cell line. They were cloned by limiting dilution. One CTL clone recognized melanoma cell lines expressing tyrosinase and the B*4002 molecule, either spontaneously or upon transfection. We demonstrated that this clone recognizes the tyrosinase-derived nonapeptide 316-324 (ADVEFCLSL) and the overlapping decapeptide 315-324 (SADVEFCLSL). We derived two distinct additional specific CTL clones from this same patient that were also reactive against B*4002 melanoma cell lines, suggesting a relative diversity of this specific repertoire in this patient. Stimulating PBMC derived from four additional B*4002 melanoma patients with the tyrosinase 316-324 nonapeptide induced the growth of specific cells for two of the patients, demonstrating the immunogenicity of this new epitope. Our data show that this nonapeptide is a new tool that could be used to generate melanoma-specific T cells for adoptive immunotherapy or serve as a peptide vaccine for HLA-B*4002 melanoma patients.
Godet
Yann
Y
INSERM U892, 9 quai Moncousu, 44093, Nantes cedex 1, France.
Bonnin
Annabelle
A
Guilloux
Yannik
Y
Vignard
Virginie
V
Schadendorf
Dirk
D
Dreno
Brigitte
B
Jotereau
Francine
F
Labarriere
Nathalie
N
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D019004:Galanin / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018076:DNA, Complementary; D000939:Epitopes; D015235:HLA-B Antigens; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; C088129:galanin-NPY chimeric peptide M88; D019004:Galanin; D014442:Monophenol Monooxygenase