Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease

Int Ophthalmol. 2007 Apr-Jun;27(2-3):87-95. doi: 10.1007/s10792-006-9020-y. Epub 2007 Jan 26.

Abstract

Aim: To determine whether T lymphocytes of patients with Vogt-Koyanagi-Harada (VKH) disease cross-react with peptides of melanocytes and with exogenous antigens.

Methods: Cross-reactivity with melanocyte peptides, tyrosinase (tyrosinase(450-462): SYLQDSDPDSFQD) and the mimic virus peptide, i.e., cytomegalovirus envelope glycoprotein H (CMV-egH(290-302): SYLKDSDFLDAAL) was examined by a lymphocyte proliferation assay or cytokine production. The seroprevalence of various viruses was examined by a complement fixation test. To examine if the virus infections in VKH patients were latent, we measured genomic DNA of the virus using real-time polymerase chain reaction (PCR).

Result: Some of the T cells established from VKH recognized melanocyte peptides including the tyrosinase peptide as well as the CMV-egH(290-302) peptide, which had a high amino acid homology to the tyrosinase peptide. Cytomegalovirus (CMV) peptide-specific T cells showed a significant proliferation not only to CMV-egH(290-302) but also to tyrosinase(450-462). The seroprevalence of CMV was significantly higher in VKH patients. In addition, all tested samples of VKH patients were negative for CMV-DNA.

Conclusions: These results indicate that CMV infection may stimulate the production of T cells that cross-react with tyrosinase by a mechanism of molecular mimicry. These events may be responsible for the onset of VKH disease.

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Complement Fixation Tests
  • Cross Reactions
  • Cytokines / biosynthesis
  • Cytomegalovirus / genetics
  • DNA, Viral / analysis
  • Genome, Viral
  • Herpesvirus 3, Human / genetics
  • Herpesvirus 4, Human / genetics
  • Humans
  • Lymphocyte Activation
  • Molecular Mimicry
  • Monophenol Monooxygenase / immunology*
  • Peptide Fragments / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seroepidemiologic Studies
  • Simplexvirus / genetics
  • T-Lymphocytes / immunology*
  • Uveomeningoencephalitic Syndrome / immunology*
  • Uveomeningoencephalitic Syndrome / virology
  • Viral Envelope Proteins / immunology*

Substances

  • Cytokines
  • DNA, Viral
  • Peptide Fragments
  • Viral Envelope Proteins
  • glycoprotein H, Cytomegalovirus
  • Monophenol Monooxygenase