Identification of an antigenic epitope in Helicobacter pylori urease that induces neutralizing antibody production

被引:54
作者
Hirota, K
Nagata, K
Norose, Y
Futagami, S
Nakagawa, Y
Senpuku, H
Kobayashi, M
Takahashi, H
机构
[1] Nippon Med Coll, Dept Microbiol & Immunol, Bunkyo Ku, Tokyo 1138602, Japan
[2] Nippon Med Coll, Dept Internal Med 3, Bunkyo Ku, Tokyo 1138602, Japan
[3] Hyogo Med Univ, Dept Bacteriol, Nishinomiya, Hyogo 6638131, Japan
[4] Natl Inst Infect Dis, Dept Oral Sci, Shinjuku Ku, Tokyo 1628640, Japan
关键词
D O I
10.1128/IAI.69.11.6597-6603.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to gain insight into how this antibody affects urease activity, the epitope that was recognized by the antibody was determined. By screening a panel of overlapping synthetic peptides covering the entire sequence of the two subunits (UreA and UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB-33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from either end allowed us to determine the minimal epitope as 8 amino acid residues (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short sequence which formed a flap over the active site of urease, suggesting that binding of the L2 antibody sterically inhibits access of urea, the substrate of urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8-mer minimal epitope resulted in generation of antiurease antibodies that were capable of inhibiting the enzymatic activity. Since urease is critical for virulence of H. pylori, antigenic peptides that induce production of antibodies to inhibit its enzymatic activity may potentially be a useful tool as a vaccine for prevention and treatment of H. pylori infection.
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页码:6597 / 6603
页数:7
相关论文
共 32 条
[1]   CONTRIBUTION OF HLA-DQA GENE TO HOSTS RESPONSE AGAINST HELICOBACTER-PYLORI [J].
AZUMA, T ;
KONISHI, J ;
TANAKA, Y ;
HIRAI, M ;
ITO, S ;
KATO, T ;
KOHLI, Y .
LANCET, 1994, 343 (8896) :542-543
[2]   PROTECTION AGAINST FOOT-AND-MOUTH-DISEASE BY IMMUNIZATION WITH A CHEMICALLY SYNTHESIZED PEPTIDE PREDICTED FROM THE VIRAL NUCLEOTIDE-SEQUENCE [J].
BITTLE, JL ;
HOUGHTEN, RA ;
ALEXANDER, H ;
SHINNICK, TM ;
SUTCLIFFE, JG ;
LERNER, RA ;
ROWLANDS, DJ ;
BROWN, F .
NATURE, 1982, 298 (5869) :30-33
[3]   NUCLEOTIDE-SEQUENCE OF 2 GENES FROM HELICOBACTER-PYLORI ENCODING FOR UREASE SUBUNITS [J].
CLAYTON, CL ;
PALLEN, MJ ;
KLEANTHOUS, H ;
WREN, BW ;
TABAQCHALI, S .
NUCLEIC ACIDS RESEARCH, 1990, 18 (02) :362-362
[4]   RAPID SOLID-PHASE SYNTHESIS OF BRADYKININ [J].
CORLEY, L ;
ANFINSEN, CB ;
SACHS, DH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1972, 47 (06) :1353-&
[5]   ORAL IMMUNIZATION WITH HELICOBACTER-PYLORI UREASE-B SUBUNIT AS A TREATMENT AGAINST HELICOBACTER INFECTION IN MICE [J].
CORTHESYTHEULAZ, I ;
PORTA, N ;
GLAUSER, M ;
SARAGA, E ;
VANEY, AC ;
HAAS, R ;
KRAEHENBUHL, JP ;
BLUM, AL ;
MICHETTI, P .
GASTROENTEROLOGY, 1995, 109 (01) :115-121
[6]   ORAL IMMUNIZATION AGAINST HELICOBACTER-PYLORI [J].
CZINN, SJ ;
NEDRUD, JG .
INFECTION AND IMMUNITY, 1991, 59 (07) :2359-2363
[7]   Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer [J].
DElios, MM ;
Manghetti, M ;
Almerigogna, F ;
Amedei, A ;
Costa, F ;
Burroni, D ;
Baldari, CT ;
Romagnani, S ;
Telford, JL ;
DelPrete, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (07) :1751-1755
[8]   ESSENTIAL ROLE OF UREASE IN PATHOGENESIS OF GASTRITIS INDUCED BY HELICOBACTER-PYLORI IN GNOTOBIOTIC PIGLETS [J].
EATON, KA ;
BROOKS, CL ;
MORGAN, DR ;
KRAKOWKA, S .
INFECTION AND IMMUNITY, 1991, 59 (07) :2470-2475
[9]   Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and induces their apoptosis [J].
Fan, XJ ;
Gunasena, H ;
Cheng, ZJ ;
Espejo, R ;
Crowe, SE ;
Ernst, PB ;
Reyes, VE .
JOURNAL OF IMMUNOLOGY, 2000, 165 (04) :1918-1924
[10]   Systemic and local immune responses against Helicobacter pylori urease in patients with chronic gastritis:: distinct IgA and IgG productive sites [J].
Futagami, S ;
Takahashi, H ;
Norose, Y ;
Kobayashi, M .
GUT, 1998, 43 (02) :168-175