A tyrosinase nonapeptide presented by HLA‐B44 is recognized on a human melanoma by autologous cytolytic T lymphocytes

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Abstract
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.