Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene.
Although commonly expressed human melanoma-associated antigens recognized by CD8+ cytolytic T cells have been described, little is known about CD4+ T-cell recognition of melanoma-associated antigens. Epstein-Barr virus-transformed B cells were used to present antigens derived from whole cell lysates of autologous and allogeneic melanomas for recognition by melanoma-specific CD4+ T-cell lines and clones cultured from tumor-infiltrating lymphocytes. HLA-DR-restricted antigens were detected in the lysates on the basis of specific release of cytokines from the responding T cells. Antigen sharing was demonstrated in the majority of melanomas tested, as well as in cultured normal melanocytes, but not in other normal tissues or nonmelanoma tumors. T-cell clones manifested a single recognition pattern, suggesting the presence of an immunodominant epitope. This epitope was identified as a product of the tyrosinase gene, which has also been shown to encode class I-restricted epitopes recognized by CD8+ T cells from melanoma patients. Identification of commonly expressed tumor-associated protein molecules containing epitopes presented by both class I and class II major histocompatibility molecules may provide optimal reagents for cancer immunization strategies.
Topalian
S L
SL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Rivoltini
L
L
Mancini
M
M
Markus
N R
NR
Robbins
P F
PF
Kawakami
Y
Y
Rosenberg
S A
SA
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014442:Monophenol Monooxygenase