ROLE OF MONOCLONAL O-ANTIGEN ANTIBODY EPITOPE SPECIFICITY AND ISOTYPE IN PROTECTION AGAINST EXPERIMENTAL MOUSE TYPHOID

ROLE OF MONOCLONAL O-ANTIGEN ANTIBODY EPITOPE SPECIFICITY AND ISOTYPE IN PROTECTION AGAINST EXPERIMENTAL MOUSE TYPHOID
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DOI:
10.1016/0882-4010(87)90019-2
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发表时间:
1987-03-01
影响因子:
3.8
通讯作者:
LINDBERG, AA
LINDBERG, AA
中科院分区:
医学3区
文献类型:
--
作者:
CARLIN, NIA;SVENSON, SB;LINDBERG, AA

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建立了一组对鼠伤寒沙门氏菌细胞被膜脂多糖的O-抗原多糖链具有特异性的14种单克隆抗体。在被动血凝和酶免疫测定中,针对一组沙门氏菌糖抗原(天然和合成)测定每个抗体克隆的特异性。单克隆抗体可分为至少五个不同的组:(i)O4表位特异性,(ii)O4,12特异性,(iii)O4,122特异性,(iv)O5特异性,和(v)O12特异性。这些特异性对应于多糖链的不同结构和构象域,并且通常延伸到聚合物的一个以上的重复单元(四糖)。这些抗体提供的被动保护作用在实验小鼠伤寒模型中使用S.鼠伤寒沙门氏菌SH2201进行腹腔内攻击。IgG3同种型的单克隆抗体可用于四个表位组,并按以下活性顺序具有保护性:O4> O4,12 ≥O4,122 mchgt. O12 O4和O12抗体之间的保护活性差异> 2500倍。IgM类的抗体是高度保护性的,无论是O4,12或O12表位特异性。两种具有O5表位特异性的IgA抗体不具有保护性。结果表明,同种型和表位特异性对于宿主产生的抗体的保护能力都是重要的。
A panel of 14 monoclonal antibodies with specificity for the O-antigenic polysaccharide chain of the lipopolysaccharide of the cell envelope of Salmonella typhimurium was established. The specificity of each antibody clone was determined against a set of Salmonella saccharide antigens, natural and synthetic, in passive hemagglutination and enzyme immunoassays. The monoclonal antibodies could be classified into at least five different groups: (i) O4 epitope specific, (ii) O4,12 specific, (iii) O4,122 specific, (iv) O5 specific, and (v) O12 specific. These specificities correspond to different structural and conformational domains of the polysaccharide chain, and often extend over more than one repeating unit (tetrasaccharide) of the polymer. The passive protection afforded by these antibodies was estimated in an experimental mouse typhoid model using S. typhimurium SH2201 for intraperitoneal challenge. Monoclonal antibodies of the IgG3 isotype were available for four of the epitope groups and were protective in the following order of activity O4 > O4,12 .gtoreq. O4,122 .mchgt. O12. The difference between O4 and O12 antibodies was > 2500 fold in protective activity. Antibodies of the IgM class were highly protective irrespective of being of the O4,12 or O12 epitope specificity. Two IgA antibodies with O5 epitope specificity were not protective. The results show that both isotype and epitope specificity can be of importance for the protective ability of antibodies generated by the host.