A nonsubstituted primary hydroxyl group in position 6' of free lipid A is required for binding of lipid A monoclonal antibodies.
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.
Brade
L
L
Department of Immunochemistry and Biochemical Microbiology, Center for Medicine and Biosciences, Research Center Borstel, Germany.
Engel
R
R
Christ
W J
WJ
Rietschel
E T
ET
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D018604:Epitope Mapping; D006878:Hydroxides; D007124:Immunoenzyme Techniques; D008050:Lipid A / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D006878:Hydroxides; D008050:Lipid A