Identification of autoreactive T cells in Vogt-Koyanagi-Harada disease

Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2004-9.

Abstract

Purpose: To determine the finer specificity and immunologic features of autoreactive T cells in Vogt-Koyanagi-Harada (VKH) disease.

Methods: T-cell clones (TCCs ) specific to tyrosinase family proteins were raised from the peripheral blood mononuclear cells (PBMCs) of patients with VKH disease, and the response of the TCCs to 30-mer peptides was determined. The TCCs that were reactive to the peptides with strong binding sites for HLA DRB1*0405 were initially tested. Then, a finer specificity of these TCCs against 12- to 14-mer peptides was determined. The cytokine production of these clones was measured by ELISA.

Results: A total of 62 stable TCCs were established from the PBMCs of five patients with VKH (28 clones against tyrosinase, 34 clones against tyrosinase-related protein [TRP]1). Five of 28 TCCs for tyrosinase and 2 of 34 for TRP1 were reactive to the 30-mer peptides with strong binding sites for HLA DRB1*0405. These seven clones showed proliferative responses to one or more of the 12- to 14-mer peptides that match the motif of the strong binding site for HLADRB1*0405. Five of seven of the TCCs may be T-helper (Th) type 1, one of the remaining TCCs may be Th0, and the other may be Th2.

Conclusions: The autoreactive T cells against tyrosinase and/or TRP1 may contribute to the development of VKH disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantigens / immunology*
  • Autoimmune Diseases / immunology*
  • Clone Cells
  • Cytokines / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • HLA-DR Antigens / metabolism
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Glycoproteins*
  • Middle Aged
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / immunology
  • Oxidoreductases*
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Proteins / chemistry
  • Proteins / immunology
  • T-Lymphocytes / immunology*
  • Uveomeningoencephalitic Syndrome / immunology*

Substances

  • Autoantigens
  • Cytokines
  • HLA-DR Antigens
  • Membrane Glycoproteins
  • Peptide Fragments
  • Proteins
  • Oxidoreductases
  • TYRP1 protein, human
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase