Identification of autoreactive T cells in Vogt-Koyanagi-Harada disease.
OBJECTIVE
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.
Gocho
K
K
Department of Ophthalmology, Akita University School of Medicine, Japan.
Kondo
I
I
Yamaki
K
K
D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000276:immunology; D010088:Oxidoreductases; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology*
D001324:Autoantigens; D016207:Cytokines; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011506:Proteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase