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S Sugita, H Takase, Y Imai, M Mochizuki; Immunopathogenic Mechanisms of a Melanocyte-specific Autoimmune Disease: A Cross-reaction Between to Tyrosinase Peptides and Cytomegalovirus Antigen . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1529.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:We reported that patients with Vogt-Koyanagi-Harada (VKH) disease had immune responses specific to human melanocyte antigens, tyrosinase and gp100. This study was aimed at analyzing whether lymphocytes of patients with VKH disease have a cross-reaction between melanocyte peptides and virus antigens. Methods:The subjects of this study were patients with VKH disease and patients with other uveitis in 1989-2001at our hospital. We searched molecular mimicry between tyrosinase450-462, gp10044-59 and exogenous antigen, such as virus, using database screening. Then, crossreactivity to melanocyte peptides and virus antigen were examined by lymphocyte proliferation assay. The seroprevalence of various viruses in patients with VKH disease (n=109) was examined by complement fixation test. In order to examine if the virus infection in VKH patients were latent, genomic DNA of virus was measured by quantitative PCR using samples from serum, cerebro-spinal fluid, and aqueous humor. All samples were obtained after informed consent was obtained. Results:In database screening, cytomegalovirus envelope glycoprotein H (CMV-egH290-302) had high amino acid homology to tyrosinase450-462 peptide. It was HLA-DRB1*0405 binding peptide. The CMV-egH290-302 peptide pulsed in HLA-DRB1*0405 transfectant LDR-4 cells were examined if T cell clones (TCCs) established from VKH patients recognized the peptide. Consequently, none of these TCCs recognized CMV-egH290-302 pulsed in LDR4. However, the CMV peptide-specific T cells showed significant proliferation to CMV-egH290-302 peptide, as well as to tyrosinase450-462. Similarly, the tyrosinase peptide-specific TCLs also proliferated in response to the two peptides. The seroprevalence of CMV was significantly higher in VKH patients (106/109, 97.3%) than in other uveitis (92/109, 84.4%) (p=0.0002). In addition, all tested samples of VKH patients were negative for CMV-DNA. Conclusion:These data first demonstrate that human melanocyte antigens, tyrosinase and gp100, are candidates of the pathogenic auto-antigens of the disease, and the mechanism of autoimmunity induced by molecular mimicry against tyrosinase might account for the CMV infection. Thus, viral infection may trigger lymphocytes of VKH patients that cross-react to self-antigens by a mechanism of molecular mimicry.
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