The relationship between the ectodomain shedding of the 180-kDa bullous pemphigoid antigen and its autoantigenicity

180kDa大疱性类天疱疮抗原胞外域脱落与其自身抗原性的关系

• 批准号: 23659547
• 负责人: HIRAKO Yoshiaki
• 金额: $ 2.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659547/
• 关键词: 表皮水疱症; 類天疱瘡; コラーゲン; 自己免疫疾患; プロセシング; ヘミデスモソーム; 自己抗体; エピトープ; プロテアーゼ

The 180-kDa bullous pemphigoid antigen (BP180) is a hemidesmosomal transmembrane protein. The ectodomain of BP180 is shed from keratinocyte cell surface by a proteolytic cleavage within the membrane-proximal non-collagenous 16th A (NC16A) domain. The autoantigen for the major type of linear IgA bullous dermatosis (LAD, lamina lucida type) is the shed ectodomain of BP180. However, why most LAD sera react with the shed ectodomain, but not with the intact BP180, is unknown. The aim of this study was to characterize the unique cleavage-dependent epitope(s) in the shed ectodomain. Four of the six LAD sera reacted mainly to the boundary region between the NC16A and the collagenous 15th (C15) domains. The results of this study indicate that the major epitopes for LAD sera is formed or exposed by a cleavage-induced conformational change, and are located at the boundary between the NC16A and C15 domains.

大疱性类天疱疮抗原(BP180)是一种半桥粒跨膜蛋白。BP180的胞外结构域通过膜近端非胶原性16A(NC16A)结构域内的蛋白水解性裂解从角质形成细胞表面脱落。线状IgA大疱性皮肤病的主要类型(LAD，光板型)的自身抗原是BP180的脱落外区。然而，为什么大多数LAD血清与脱落的胞外结构域反应，而不与完整的BP180反应，这一点尚不清楚。本研究的目的是对脱落胞外区中唯一的切割依赖表位(S)进行特征分析。6份LAD血清中有4份主要与NC16A和C15胶原区交界处发生反应。本研究的结果表明，LAD血清的主要表位是通过切割诱导的构象变化而形成或暴露的，并位于NC16A和C15结构域之间。

项目成果

A case of concurrent anti-laminin γ1 pemphigoid and anti-laminin 332-type mucous membrane pemphigoid

抗层粘连蛋白γ1型类天疱疮与抗层粘连蛋白332型粘膜类天疱疮并发1例

• DOI: 10.1111/bjd.13113
• 发表时间: 2014
• 期刊: Br J Dermatol
• 作者: Li X;Qian H;Ishii N;Yamaya M;Fukuda H;Mukai H;Hirako Y;and Hashimoto T
• 通讯作者: and Hashimoto T

眼型粘膜類天疱瘡

眼粘膜类天疱疮

• 发表时间: 2013
• 期刊: Visual Dermatology
• 作者: Kanwar AJ;Tsuruta D;Vinay K;Koga H;Ishii N;Dainichi T;Hashimoto T.;十亀良介
• 通讯作者: 十亀良介

Isolation of mouse monoclonal antibodies reactive with maturation-related unique epitope(s) on human type VII collagen

与人 VII 型胶原上成熟相关的独特表位发生反应的小鼠单克隆抗体的分离

• 发表时间: 2012
• 作者: Taihei Hayakawa;Yoshiaki Hirako;et al.
• 通讯作者: et al.

An epithelial isoform of LMO7 interacts with actin cytoskeleton through a novel functional region at its N-terminus

LMO7 的上皮亚型通过其 N 末端的新功能区域与肌动蛋白细胞骨架相互作用

• 发表时间: 2012
• 作者: Tomoe Yamauchi; Katsushi Owaribe; Yuji Nishizawa;Yoshiaki Hirako
• 通讯作者: Yoshiaki Hirako

Preparation of the hemidesmosome-rich fraction from a human squamous cell carcinoma line DJM-1

人鳞状细胞癌细胞系 DJM-1 富含半桥粒组分的制备

• 发表时间: 2011
• 作者: 平子善章;米元裕貴;尾張部克志
• 通讯作者: 尾張部克志