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.