Melanocyte lineage-specific antigen gpl00 is recognized by melanoma-derived tumor-infiltrating lymphocytes

We recently isolated a cDNA clone that encodes the melanocyte lineage-specific antigen glycoprotein (gp)100. Antibodies directed against gpl00 are an important tool in the diagnosis of human melanoma. Since the gpl00 antigen is highly expressed in melanocytic cells, we investigated whether this antigen might serve as a target for antimelanoma cytotoxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-infiltrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200) are directed against gpl00. HLA-A2.1⁺ melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expressing both HLA-A2.1 and gpl00, are lysed by TIL 1200, whereas transfectants expressing only HLA-A2.1 are not susceptible to lysis. Furthermore, the HLA-A2.1⁺ melanoma cell line BLM, which lacks gpl00 expression and is resistant to lysis, becomes susceptible after transfection of gpl00 cDNA. Finally, HLAA2.1⁺ normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation antigen gpl00 can be recognized in the context of HLA-A2.1 by CTL from a melanoma patient. Gpl00 may therefore constitute a useful target for specific immunotherapy against melanoma, provided that no unacceptable cytotoxicity towards normal tissue is observed.