Project/Area Number |
13670481
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内科学一般
|
Research Institution | Nippon Medical School |
Principal Investigator |
TAKAHASHI Hidemi Nippon Medical School, Dept. of Microbiol. & Immunol., Professor and Chairman, 大学院・医学研究科, 教授 (40221361)
|
Project Period (FY) |
2001 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | 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 |
Research Abstract |
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.
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