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 express ed on melanocytes and the retina, We have investigated whether Vogt-Ko yanagi-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 o f three patients with VKH disease and one patient with SO, CD8(+) T ce ll 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 manne r, These CD8(+) TCC lysed both melanocytes and melanoma cells in a HLA -AP-restricted manner, In addition, CD8(+) TCC recognizing a HLA-A2-bi nding MART-1 peptide were also established from peripheral blood monon uclear cells of a patient with VKH disease, In contrast, either CD4(+) TCC from these patients or CD8(+) TCC from the intraocular fluid of H LA-A2(+) patients with uveitis associated with Behcet's disease or HTL V-I uveitis did not show this cytotoxicity, The results demonstrate th at the MART-1 peptide-specific cytotoxic T lymphocytes lyse melanocyte s in the eye of patients with VKH disease or SO, suggesting that these diseases are autoimmune diseases directed toward the MART-1 antigen i n HLA-A2(+) patients.