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

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Abstract
The MART-1/Melan-A melanoma antigen recognized by the majority of HLA-A2-restricted 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-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.

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