A nonsubstituted primary hydroxyl group in position 6' of free lipid A is required for binding of lipid A monoclonal antibodies

被引:15
作者
Brade, L
Engel, R
Christ, WJ
Rietschel, ET
机构
[1] RES CTR BORSTEL,CTR MED & BIOSCI,DEPT IMMUNOCHEM & BIOCHEM MICROBIOL,D-23845 BORSTEL,GERMANY
[2] EISAI RES INST,ANDOVER,MA
关键词
D O I
10.1128/IAI.65.9.3961-3965.1997
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lipid A monoclonal antibodies, which require for binding the presence of the bisphosphorylated D-glucosamine disaccharide lipid A backbone, were tested against synthetic lipid A precursor Ia and compound B 1047 by enzyme immunoassay. The last-named compound is a precursor Ia analog with a methoxy instead of a hydroxy group at C6' and was chosen to determine why these antibodies failed to recognize the bound lipid A present in lipopolysaccharide (LPS). Whereas all antibodies tested bound to precursor Ia, none of them bound to compound B 1047 or Escherichia coli Re LPS to a significant extent. Compared to the natural substituent at C6', i.e., 3-deoxy-D-manno-octulosonic acid (Kdo), the methoxy group is neither bulky nor charged. Thus, the data suggest that it is not hindrance by Kdo but rather the generation of a neoantigen that endows lipid A with immunoreactivity upon liberation from LPS by acid hydrolysis.
引用
收藏
页码:3961 / 3965
页数:5
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