Immune response to chemically modified flagellin. I. Induction of antibody tolerance to flagellin by acetoacetylated derivatives of the protein.
Flagellin (mol. wt. 40,000) from S. adelaide organisms was acetoacetylated to varying extents with diketene (acetoacetic anhydride). Chemical studies demonstrated that the amino groups of flagellin were more readily acetoacetylated than the hydroxyl groups. Several antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies. Loss in antigenic activity following acetoacetylation was not related to the number of acetoacetyl groups attached but was determined by the type of residue substituted. Reactive lysine residues were much less important anti-genically than easily substituted hydroxyl groups. Acetoacetylation very readily destroyed the antibody-forming capacity of flagellin in rats. This fall in immunogenicity was related to the antigenic activity of the preparations. In fact, only a 40% reduction in the antigenic activity of flagellin produced a 90-95% reduction in primary antibody formation. The more heavily acetoacetylated flagellins produced no detectable antibody and, in fact, rendered adult rats tolerant (in terms of antibody formation) to a subsequent challenge of flagellin. Tolerance was induced by acetoacetylated flagellins which had drastically reduced affinities for anti-flagellin antibodies. These results were interpreted as indicating that the affinity of antigen for receptors on cells appears to be of crucial importance in determining whether antibody formation or immunological tolerance (antibody suppression) occurs.
D000090:Acetoacetates / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D000941:Antigens; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001665:Binding Sites; D005260:Female; D007108:Immune Tolerance; D007120:Immunochemistry; D005779:Immunodiffusion; D008297:Male; D011817:Rabbits; D051381:Rats; D012475:Salmonella / Q000276:immunology*
D000090:Acetoacetates; D000941:Antigens; D000942:Antigens, Bacterial; D001426:Bacterial Proteins