Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens
Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens
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DOI：
10.1167/iovs.05-1547
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Mochizuki, Manabu
中科院分区：
文献类型：
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作者：
Sugita, Sunao;Takase, Hiroshi;Mochizuki, Manabu
目的.为了确定Vogt-Koyanagi-Harada（VKH）病患者是否具有对黑素细胞抗原酪氨酸酶和gp 100的特异性免疫应答。T细胞克隆（TCC）建立从细胞浸润的房水和外周血单核细胞（PBMC）的VKH患者。靶细胞是LDR 4转染的细胞（HLA-DRB 1 *0405）。在酪氨酸酶（酪氨酸酶（450-462）：SYLQDSDPDSFQD）、gp 100（9000（44-59）：WN-RQLYPEWTEAQRLD）或对照肽存在下，将TCC与LDR 4共培养。通过细胞因子的产生来评价免疫应答。响应的黑素细胞肽特异性VKH-TCC的特征在于通过免疫荧光方法与流式细胞术。通过数据库筛选，在酪氨酸酶450 -462、gp 100（44-59）和外源抗原（如病毒）中进行分子模拟搜索。在HLA-DR 4（+）（HLA-DRB 1 *0405，0410）VKH患者中，浸润眼睛和PBMC的细胞含有一群CD 4（+）T淋巴细胞，其识别酪氨酸酶和gp 100肽，并产生RANTES和IFN-γ以响应这两种肽。T细胞是主动记忆性Th 1型淋巴细胞，它们识别酪氨酸酶肽并响应HfA-DRB 1 *0405（+）黑素瘤细胞产生IFN-γ。CMV包膜糖蛋白H（CMV-egH（290-302））与酪氨酸酶肽段具有高度的氨基酸同源性。此外，部分VKH-TCC还能识别CMV-egH（290-302）肽和酪氨酸酶肽。在VKH有酪氨酸酶和-gp 100肽特异性T细胞，可以介导炎症反应。这种黑素细胞抗原特异性T细胞可能与VKH疾病的病因和病理学有关。
PURPOSE. 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 (tyrosinase(450-462): SYLQDSDPDSFQD), gp100 (9000(44-59): WN-RQLYPEWTEAQRLD), 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 HfA-DRB1*0405(+) melanoma cells. Cytornegalovirus envelope glycoprotein H (CMV-egH(290-302)) had high amino acid homology with the tyrosinase peptide. In addition, some of the VKH-TCCs recognized CMV-egH(290-302) 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.