Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
OBJECTIVE
To determine whether patients with Vogt-Koyanagi-Harada (VKH) disease have immune responses specific to the melanocyte antigens tyrosinase and gp100.


METHODS
T-cell clones (TCCs) were established from cells infiltrating the aqueous humor and from peripheral blood mononuclear cells (PBMCs) of patients with VKH. The target cells were LDR4-transfected cells (HLA-DRB1*0405). The TCCs were cocultured with LDR4 in the presence of tyrosinase (tyrosinase450-462: SYLQDSDPDSFQD), gp100 (gp100(44-59): WNRQLYPEWTEAQRLD), or a control peptide. The immune response was evaluated by cytokine production. The responding melanocyte peptide-specific VKH-TCCs were characterized by an immunofluorescence method with flow cytometry. A search was made for molecular mimicry among tyrosinase450-462, gp100(44-59), and exogenous antigens, such as viruses, by database screening.


RESULTS
Cells infiltrating the eye and PBMCs in HLA-DR4+ (HLA-DRB1*0405, 0410) patients with VKH contained a population of CD4+ T lymphocytes that recognized tyrosinase and gp100 peptides and produced RANTES and IFN-gamma in response to the two peptides. The T cells were active memory Th1-type lymphocytes, and they recognized the tyrosinase peptide and produced IFN-gamma in response to HLA-DRB1*0405+ melanoma cells. Cytomegalovirus envelope glycoprotein H (CMV-egH290-302) had high amino acid homology with the tyrosinase peptide. In addition, some of the VKH-TCCs recognized CMV-egH290-302 peptide, as well as the tyrosinase peptides.


CONCLUSIONS
In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response. Such melanocyte antigen-specific T cells could be associated with the cause and pathology of VKH disease.
Sugita
Sunao
S
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan. sunaoph@tmd.ac.jp
Takase
Hiroshi
H
Taguchi
Chikako
C
Imai
Yasuhisa
Y
Kamoi
Koju
K
Kawaguchi
Tatsushi
T
Sugamoto
Yoshiharu
Y
Futagami
Yuri
Y
Itoh
Kyogo
K
Mochizuki
Manabu
M
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007498:Iris / Q000378:metabolism; D008544:Melanocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000378:metabolism; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics / Q000276:immunology*; D058951:gp100 Melanoma Antigen
D016207:Cytokines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C493960:HLA-DRB1*04:05 antigen; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase