Sugita Sunao, Takase Hiroshi, Kawaguchi Tatsushi, Taguchi Chikako, Mochizuki Manabu
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Int Ophthalmol. 2007 Apr-Jun;27(2-3):87-95. doi: 10.1007/s10792-006-9020-y. Epub 2007 Jan 26.
To determine whether T lymphocytes of patients with Vogt-Koyanagi-Harada (VKH) disease cross-react with peptides of melanocytes and with exogenous antigens.
Cross-reactivity with melanocyte peptides, tyrosinase (tyrosinase(450-462): SYLQDSDPDSFQD) and the mimic virus peptide, i.e., cytomegalovirus envelope glycoprotein H (CMV-egH(290-302): 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).
Some of the T cells established from VKH recognized melanocyte peptides including the tyrosinase peptide as well as the CMV-egH(290-302) 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-egH(290-302) but also to tyrosinase(450-462). The seroprevalence of CMV was significantly higher in VKH patients. In addition, all tested samples of VKH patients were negative for CMV-DNA.
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.
确定伏格特-小柳-原田(VKH)病患者的T淋巴细胞是否与黑素细胞肽及外源性抗原发生交叉反应。
通过淋巴细胞增殖试验或细胞因子产生情况,检测与黑素细胞肽、酪氨酸酶(酪氨酸酶(450 - 462):SYLQDSDPDSFQD)以及模拟病毒肽即巨细胞病毒包膜糖蛋白H(CMV-egH(290 - 302):SYLKDSDFLDAAL)的交叉反应。通过补体结合试验检测各种病毒的血清流行率。为检测VKH患者的病毒感染是否处于潜伏状态,我们使用实时聚合酶链反应(PCR)测量病毒的基因组DNA。
从VKH患者分离出的一些T细胞识别包括酪氨酸酶肽在内的黑素细胞肽以及与酪氨酸酶肽具有高度氨基酸同源性的CMV-egH(290 - 302)肽。巨细胞病毒(CMV)肽特异性T细胞不仅对CMV-egH(290 - 302)有显著增殖反应,对酪氨酸酶(450 - 462)也有显著增殖反应。VKH患者中CMV的血清流行率显著更高。此外,所有检测的VKH患者样本的CMV-DNA均为阴性。
这些结果表明,CMV感染可能通过分子模拟机制刺激产生与酪氨酸酶发生交叉反应的T细胞。这些事件可能是VKH病发病的原因。