Skip to main content

Advertisement

Log in

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

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

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 (tyrosinase450–462: SYLQDSDPDSFQD) and the mimic virus peptide, i.e., cytomegalovirus envelope glycoprotein H (CMV-egH290–302: 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-egH290–302 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-egH290–302 but also to tyrosinase450–462. 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

APCs:

Antigen presenting cells

CMV:

Cytomegalovirus

EBV:

Epstein–Barr virus

HSV:

Herpes simplex virus

PBMCs:

Peripheral blood mononuclear cells

TCLs:

T cell lines

VKH:

Vogt-Koayanagi Harada

VZV:

Varicella zoster virus

References

  1. Lubin JR, Ni C, Albert DM (1982) Clinicopathological study of the Vogt–Koyanagi–Harada syndrome. Int Ophthalmol Clin 22:141–146

    Article  PubMed  CAS  Google Scholar 

  2. Shindo Y, Inoko H, Yamamoto T, et al (1994) HLA-DRB1 typing of Vogt–Koyanagi–Harada’s disease by PCR-RFLP and the strong association with DRB1*0405 and DRB1*0410. Br J Ophthalmol 78:223–226

    PubMed  CAS  Google Scholar 

  3. Hammer H (1974) Cellular hypersensitivity to uveal pigment confirmed by leukocyte migration tests in sympathetic ophthalmia and the Vogt–Koyanagi–Harada syndrome. Br J Ophthalmol 58:773–776

    PubMed  CAS  Google Scholar 

  4. Read RW, Rao NA, Cunningham ET (2000) Vogt–Koyanagi–Harada disease. Curr Opin Ophthalmol 11:437–442

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan MH, Meyeserian M (1962) An immunological cross-reaction between group A streptococcal cells and human heart tissue. Lancet 1:706–710

    Article  PubMed  CAS  Google Scholar 

  6. Michael B, Oldstone A (1987) Molecular mimicry and autoimmune disease. Cell 50:819–820

    Article  Google Scholar 

  7. Fujinami RS, Oldstone MBA (1985) Amino acid homology and immune response between the encephalitogenic site of myelin basic protein and virus: a mechanism for autoimmunity. Science 230:1043–1045

    Article  PubMed  CAS  Google Scholar 

  8. Ferrari I, Levin MJ, Wallkat G, et al (1995) Molecular mimicry between the immunodominant ribosomal protein PO of Trypanosoma crusi and a functional epitope on the human b1-adrenergic receptor. J Exp Med 182:59–65

    Article  PubMed  CAS  Google Scholar 

  9. Shimoda S, Nakamura M, Ishibash H, et al (1995) HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases. J Exp Med 181:1835–1845

    Article  PubMed  CAS  Google Scholar 

  10. Albani S, Carson D (1996) A multistep molecular mimicry hypothesis for the pathogenesis of rheumatoid arthritis. Immunol Today 17:466–470

    Article  PubMed  CAS  Google Scholar 

  11. Zhao Z, Granucci S, Yeh F, et al (1998) Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 279:1344–1353

    Article  PubMed  CAS  Google Scholar 

  12. Bassili SS, Peyman GA, Gebhardt BM, et al (1996) Detection of Epstein–Barr virus DNA by polymerase chain reaction in the vitreous from a patient with Vogt–Koyanagi–Harada syndrome. Retina 16:160–161

    Article  PubMed  CAS  Google Scholar 

  13. Sugita S, Takase H, Taguchi C, et al (2006) Ocular infiltrating CD4+ T cells from patients with Vogt–Koyanagi–Harada disease recognize human melanocyte antigens. Invest Ophthalmol Vis Sci 47:2547–2554

    Article  PubMed  Google Scholar 

  14. Read RW, Holland GN, Rao NA, et al (2001) Revised diagnostic criteria for Vogt–Koyanagi–Harada disease: report of an international committee on nomenclature. Am J Ophthalmol 131:647–652

    Article  PubMed  CAS  Google Scholar 

  15. Rammensee HG, Friede T, Stevanovic S (1995) MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228

    Article  PubMed  CAS  Google Scholar 

  16. Hill CM, Liu A, Marshall KW, et al (1994) Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401. J Immunol 152:2890–2898

    PubMed  CAS  Google Scholar 

  17. Shichijo S, Nakao M, Imai Y, et al (1998) A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes. J Exp Med 187:277–288

    Article  PubMed  CAS  Google Scholar 

  18. Kimura H, Morita M, Yabuta Y, et al (1999) Quantitative analysis of Epstein–Barr virus load by using a real-time PCR assay. J Clin Microbiol 37:132–136

    PubMed  CAS  Google Scholar 

  19. Linhares MI, de Andrade GP, Tateno S, et al (1989) Prevalence of cytomegalovirus antibodies in Brazilian and Japanese populations in the north-east of Brazil. Microbiol Immunol 33:975–980

    PubMed  CAS  Google Scholar 

  20. Topalian SL, Gonzales MI, Parkhurst M, et al (1996) Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. J Exp Med 183:1965–1970

    Article  PubMed  CAS  Google Scholar 

  21. Wildner G, Diedrichs-Mohring M, Thurau SR (2002) Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin. Eur J Immunol 32:299–306

    Article  PubMed  CAS  Google Scholar 

  22. Singh VK, Kalra HK, Yamaki K, et al (1990) Molecular mimicry between uveitopathogenic site of S-antigen and viral peptides. J Immunol 144:1282–1287

    PubMed  CAS  Google Scholar 

  23. Rasmussen L (1990) Immune response to human cytomegalovirus infection. Curr Top Microbiol Immunol 154:221–254

    PubMed  CAS  Google Scholar 

  24. Chou S (1992) Molecular epidemiology of envelope glycoprotein H of human cytomegalovirus. J Infect Dis 166:604–607

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sunao Sugita.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugita, S., Takase, H., Kawaguchi, T. et al. Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int Ophthalmol 27, 87–95 (2007). https://doi.org/10.1007/s10792-006-9020-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-006-9020-y

Keywords

Navigation