Identification of autoantigens in Vogt-Koyanagi-Harada disease using recombinant retrovirus encoding melanocyte-specitic antigen genes

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Vogt-Koyanagi-Harada disease (VKH) appears to be an autoimmune disease against melanocytes. Inflammatory nature of the uveitis and a significant association with HLA-DRB1*0405 suggest that CD4+ T cells reactive to melanocyte-specific proteins presented by HLA-DRB1*0405 are involved in the development of VKH. We have been identified many melanoma antigens recognized by tumor infiltrating T lymphocytes, including melanosomal antigen (tyrosinase, TRP1, TRP2, gp100, and MART1). In the immunotherapy for patients with melanoma, skin depigmentation sometimes occurs and correlates with melanoma regression, suggesting that these antigens are also involved in autoimmune responses to melanocytes. To identify VKH-specific autoantigens, we have analyzed T cell responses against melanocytes in VKH. T cells stimulated with melanocytes in choroid plexus may be enriched in cerebrospinal fluids. We initially attempted to generate some of T cell lines and clones from lymphocytes in cerebrospinal fluids of VKH patients. Total of 61 T cell clones were isolated from 3 VKH patients by the limiting dilution method. 24 clones from a patient recognized lysate from cultured melanoma cell line (Skmel23) in an HLA- DR restricted manner. Their responses against 293IMDR1 or 293CIITA co-transfected with HLA-DRB1*0405 and various melanocyte-specific antigen cDNAs were evaluated. KU-MEL-1 was recognized by one T cell line and one clone in HLA-DRB1*0405 restricted manner. Furthermore, IgG antibodies against KU-MEL-1 were detected in the sera from 15 of 26 (58%) VKH patients. Therefore KU-MEL-1 may be involved in development of VKH as one of the auto antigens recognized by CD4+ T cells. Identification of auto antigens recognized by T cells may lead to understanding of the pathological process involved in VKH as well as to development of new diagnostic and therapeutic methods for VKH patients.