Identification of autoantigens recohnized by auto-react T cells in Vogt-Koyanagi-Harada disease

沃格特-小柳-原田病中自身反应 T 细胞识别的自身抗原的鉴定

• 批准号: 10671655
• 负责人: SUZUKI Saburousuke
• 金额: $ 2.43万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671655/
• 关键词: Vogt-Koyanagi-Harada; Melanosome protein; SEREX

Vogt-Koyanagi-Harada disease (VKH) may be caused by autoimmune responses against melanocytes in various tissues. Since the mechanism for development of VKH has not been clear yet, we attempted to identify the autoantigens. To identify antigens, we used sera that might contain specific antibodies for the VKH antigens. Although Western blot analysis did not show VKH specific bands, by immunoprecipitation analysis, a 46 kDa band was observed in melanoma cells, Skme123, but not in K562 cells, with sera from VKH, but not with sera from healthy individual, suggesting that this protein may be associated with VKH. An expression cDNA library from Skme123 was screened with sera from 7 VKH, and 26 genes were isolated. However, melanocyte specific antigen was not identified. The cDNA clones obtained with sera from 2 patients were identified to be lens epithelium derived growth factor. The antibody for this protein was detected in 4 of 12 VKH and 3 of 6 healthy individuals, suggesting that this protein might not be associated with VKH. Increased mononuclear cells in cerebrospinal fluid may contain T cells reacted to melanocytes in choroid plexus of brain. We cloned T cells from cerebrospinal fluid of VKH. The T cell clones recognized proteins from melanocytes and melanoma, but not those from nonmelanocytic cells. This reaction was blocked by anti-DR antibody, and the significant association of VKH with HLA-DRB*0405 and DQB1*0401 was reported. Therefore, these results suggested that HLA-DR restricted CD4+ T cells specific for melanocytes may be involved in the development of VKH.

Vogt-Koyanagi-Harada病（VKH）可能是由各种组织中针对黑素细胞的自身免疫反应引起的。由于VKH的发生机制尚不清楚，我们试图鉴定自身抗原。为了鉴定抗原，我们使用了可能含有VKH抗原特异性抗体的血清。虽然Western印迹分析未显示VKH特异性条带，但通过免疫沉淀分析，在黑色素瘤细胞Skme 123中观察到46 kDa条带，但在K562细胞中未观察到，用来自VKH的血清，但用来自健康个体的血清，提示该蛋白可能与VKH相关。用7株VKH的血清筛选Skme123的表达cDNA文库，共分离到26个基因。然而，黑素细胞特异性抗原未被鉴定。从2例患者血清中获得的cDNA克隆经鉴定为透镜上皮源性生长因子。在12例VKH中的4例和6例健康个体中的3例中检测到该蛋白的抗体，表明该蛋白可能与VKH无关。脑脊液中增加的单个核细胞可能含有与脑脉络丛中的黑素细胞反应的T细胞。我们从VKH的脑脊液中克隆了T细胞。T细胞克隆识别来自黑素细胞和黑素瘤的蛋白质，但不识别来自非黑素细胞的蛋白质。该反应被抗DR抗体阻断，并且报道了VKH与HLA-DRB * 0405和DQB 1 * 0401的显著关联。因此，这些结果表明，HLA-DR限制性的黑素细胞特异性的CD4 + T细胞可能参与VKH的发展。

项目成果

Suzuki S: "Quantitative evaluation of " Sunset Glow" fundus in Vogt-Kiyanagi-Harada disease"Jpn.J. Ophthalmol. 43. 327-333 (1999)

铃木S：“Vogt-Kiyanagi-Harada病中“日落辉光”眼底的定量评估”Jpn.J.

Kawakami Y et al: "T cell responses to melanoma and melanocytes"Pigment Cell Research. (in press).

Kawakami Y 等人：“T 细胞对黑色素瘤和黑色素细胞的反应”色素细胞研究。

Suzuki S: "Quantititative evaluation of "Sunset Glow" fundus i Vogt-Koyanagi-Harada disease"Jap. J. Ophthalmol. 43. 327-333 (1999)

铃木 S：“Vogt-Koyanagi-Harada 病中“日落辉光”眼底的定量评估”Jap。

Kawakami Y. Y. Suzuki, T. Shofuda, Y. Kiniwa, T. Inozume, K. Dan, T. Sakurai and T. Fujita: "T cell responses to melanoma and melanocytes"Pigment Cell Research. (in press).

Kawakami Y. Y. Suzuki、T. Shofuda、Y. Kiniwa、T. Inozume、K. Dan、T. Sakurai 和 T. Fujita：“T 细胞对黑色素瘤和黑色素细胞的反应”色素细胞研究。