Melanocyte lysis by cytotoxic T lymphocytes recognizing the MART-1 melanoma antigen in HLA-A2 patients with Vogt–Koyanagi–Harada disease

The MART-1/Melan-A melanoma antigen recognized by the majority of HLA-A2-restri cted tumorinfiltrating lymphocytes is a self antigen expressed on melanocytes and the retina. We have investigated whether Vogt-Koyanagi-Harada (VKH) disease and sympathetic ophthalmia (SO), systemic inflammatory disorders affecting various organs containing melanocytes, are autoimmune diseases directed toward the MART-1 antigen. In two of three patients with VKH disease and one patient with SO, CD8+ T cell clones (TCC) from intraocular fluid of HLA-A2+ patients lysed T2 cells when pulsed with a HLA-A2-binding MART-1 peptide, but not a HLA-A2-binding pMel-17 or tyrosinase peptide, in a HLA-A2-restricted manner. These CD8+ TCC lysed both melanocytes and melanoma cells in a HLA-A2-restricted manner. In addition, CD8+ TCC recognizing a HLA-A2binding MART-1 peptide were also established from peripheral blood mononuclear cells of a patient with VKH disease. In contrast, either CD4+ TCC from these patients or CD8+ TCC from the intraocular fluid of HLA-A2 + patients with uveitis associated with Behcet's disease or HTLV-I uveitis did not show this cytotoxicity. The results demonstrate that the MART-1 peptide-specific cytotoxic T lymphocytes lyse melanocytes in the eye of patients with VKH disease or SO, suggesting that these diseases are autoimmune diseases directed toward the MART-1 antigen in HLA-A2+ patients.