Protection against the staphylococcal enterotoxin-induced intestinal disorder in the monkey by anti-idiotypic antibodies.
The staphylococcal enterotoxin serotype B (SEB)-induced enteric intoxication and the immediate-type reaction in the skin of unsensitized monkeys was used to define whether agents competing with SEB for target cell receptors may inhibit pathophysiological effects. For this purpose a duodenal provocation test was developed by use of a pediatric gastroscope, allowing the evaluation of the influence of antagonists on the intestinal disorder upon SEB challenge at the same duodenal site. First, carboxymethylation of histidine residues of SEB caused a complete loss of emetic and skin-sensitizing activity without changing the immunological specificity. However, carboxymethylated SEB is a strong inhibitor of enteric intoxications and immediate-type skin reactions upon SEB challenge. Second, after immunization of BALB/c mice with monoclonal anti-SEB antibodies, monoclonal antiidiotypic antibodies (anti-Id) were obtained by the "hybridoma technique" and purification by idiotype-affinity chromatography. Anti-Id specifically inhibited the binding of horseradish peroxidase-labeled anti-SEB to the ligand, and SEB blocked as well the interaction of these two antibody species, indicating a high degree of binding-site selectivity. Anti-Id completely protected against emetic response and diarrhea upon duodenal provocation with SEB and inhibited immediate-type skin reactions as well. Further, anti-Id acted as an antagonist without triggering biologic functions themselves. This shows that anti-Id constitute a useful tool to protect against a bacterial toxin-induced intestinal disorder.
Reck
B
B
Max-Planck-Institut für Immunbiologie, Freiburg, Federal Republic of Germany.
Scheuber
P H
PH
Londong
W
W
Sailer-Kramer
B
B
Bartsch
K
K
Hammer
D K
DK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004768:Enterotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007130:Immunoglobulin Idiotypes; D007167:Immunotherapy; D007410:Intestinal Diseases / Q000517:prevention & control*; D008252:Macaca fascicularis; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; C031818:enterotoxin B, staphylococcal