Immune response of rabbits to lipid A: influence of immunogen preparation and distribution of various lipid A specificities.
Sixty-two rabbit anti-lipid A serum samples were compared with respect to the immunogens used (synthetic lipid A and partial structures, natural lipid A, or acid-treated bacteria). Immunoglobulin (Ig) type-specific differences in rabbit response between liposomal membrane-embedded (LME) and other lipid A immunogens were found: LME lipid A elicited predominantly IgM antibodies. Previous findings of equally good immune responses to synthetic lipid A and acid-treated bacteria (L. Brade, E.T. Rietschel, S. Kusumoto, T. Shiba, and H. Brade, Infect. Immun. 51:110-114, 1986, and L. Brade, E.T. Rietschel, S. Kusumoto, T. Shiba, and H. Brade, Prog. Clin. Biol. Res. 231:75-97, 1987) turned out to be restricted to complement-fixing antibodies; IgG titers of sera against free lipid A (whether synthetic or natural) were significantly lower than those raised with bacteria. The results indicated an increase in IgG content of sera from LME lipid A over other free lipid A immunogens to acid-treated bacteria. These data underline the importance of the physicochemical environment for the immunogenicity of lipid A. As a second objective, the presence of various lipid A antibody specificities was tested with synthetic lipid A antigens. Antibodies to monophosphoryl lipid A were detected only in sera raised with monophosphoryl immunogens. Reactivity with monosaccharide partial structures of lipid A was found both in sera against monophosphoryl lipid A and in 60% of sera against bisphosphoryl lipid A. In the former, monosaccharide reactivity was of a magnitude similar to that of reactivity with lipid A; in sera against bisphosphoryl lipid A, it was lower. No reactivity or only marginal reactivity was found with phosphate-free lipid A, thus emphasizing the role of phosphate substitution for the lipid A epitopes recognized.
Kuhn
H M
HM
Division of Biochemical Microbiology, Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, Germany.
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000939:Epitopes / Q000032:analysis*; D006461:Hemolysis; D007106:Immune Sera / Q000276:immunology; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008050:Lipid A / Q000276:immunology*; D008623:Mercaptoethanol / Q000494:pharmacology; D011817:Rabbits
D000907:Antibodies, Bacterial; D000939:Epitopes; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D008623:Mercaptoethanol