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-AP-restricted tumor-infiltrating 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 (ICC) 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-AP-restricted manner, These CD8(+) TCC lysed both melanocytes and melanoma cells in a HLA-AP-restricted manner, In addition, CD8(+) TCC recognizing a HLA-A2-binding 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.