权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of antigenic epitope for neutralizing antibody that inhibits enzymatic activity of Helicobacter pylori urease

抑制幽门螺杆菌脲酶酶活性的中和抗体抗原表位的鉴定

基本信息

批准号：
13670481
负责人：
TAKAHASHI Hidemi
金额：
$ 2.18万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670481/
关键词：
Helicobacter pylori urease neutralizing antibody epitope MAP mapping vaccine enzymatic activity Helicobacter pylori vaccine Hybridoma エピトープ合成ペプチド

项目摘要

There may be two types of Helicobacter pylori (H.pylori) urease-specific antibodies, one is unfavorable to the body in progressing gastritis and the other is benefical in preventing bacterial growth and attachment to the gastric mucosa. To find the epitope for the latter type, a series of overlapping peptides were synthesized to identify the epitope of a mouse monoclonal antibody (mAb), termed L2, which has the capacity to generate complete suppression of the enzymatic activity of H. pylori urease. Among 79 overlapping peptides tested, a predominant epitope, UB-33 (aa 321-339; CHHLDKSIKEDVQFADSRI), was identified. Immunization with KLH-conjugated UB-33 induced UB-33-specific antibody which partially abrogated the urease activity. The minimal epitope of L2 was F8 (SIKEDVQF), whereas 6-mer peptide (KEDVQF) was the minimum for UB-33-specific rabbit sera. F8-based multiple antigenic peptides (MAP) generated UB-33-specific antibody that was much stronger than UB-33 but less potent than L2 and its minimal epitope was 6-mer (SIKEDV). The amino acid 329K seems to be critical to the L2-specific antibody response. The findings shown here provide important information on making a neutralizing vaccine to prevent H.pylori infection as well as its persistency in the stomach.

幽门螺杆菌（Helicobacter pylori，H.pylori）的尿素酶特异性抗体可能有两种类型，一种是对进行性胃炎的机体不利的，另一种是有益于防止细菌生长和附着在胃粘膜上的。为了找到后一种类型的表位，合成了一系列重叠肽以鉴定小鼠单克隆抗体（mAb）的表位，称为L2，其具有产生完全抑制H的酶活性的能力。幽门螺杆菌尿素酶。在检测的79种重叠肽中，鉴定出一种主要表位UB-33（aa 321-339; CHHLDKSIKEDVQFADSRI）。用KLH结合的UB-33免疫诱导UB-33特异性抗体，其部分消除了尿素酶活性。L2的最小表位是F8（SIKEDVQF），而6-mer肽（KEDVQF）是UB-33特异性兔血清的最小表位。基于F8的多抗原肽（MAP）产生的UB-33特异性抗体比UB-33强得多，但效力低于L2，其最小表位为6聚体（SIKEDV）。氨基酸329 K似乎对L2特异性抗体应答至关重要。这里显示的发现提供了重要的信息，使中和疫苗，以防止幽门螺杆菌感染，以及其在胃中的持久性。