Reck B, Scheuber P H, Londong W, Sailer-Kramer B, Bartsch K, Hammer D K
Max-Planck-Institut für Immunbiologie, Freiburg, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1988 May;85(9):3170-4. doi: 10.1073/pnas.85.9.3170.
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.
利用葡萄球菌B型肠毒素（SEB）诱导未致敏猴子出现肠中毒和皮肤速发型反应，来确定与SEB竞争靶细胞受体的物质是否可抑制病理生理效应。为此，利用儿童胃镜开发了十二指肠激发试验，可评估拮抗剂对在同一十二指肠部位受到SEB攻击时肠道紊乱的影响。首先，SEB组氨酸残基的羧甲基化导致催吐和皮肤致敏活性完全丧失，而免疫特异性未改变。然而，羧甲基化的SEB是SEB攻击后肠中毒和皮肤速发型反应的强抑制剂。其次，用单克隆抗SEB抗体免疫BALB/c小鼠后，通过“杂交瘤技术”获得单克隆抗独特型抗体（抗Id），并通过独特型亲和层析进行纯化。抗Id特异性抑制辣根过氧化物酶标记的抗SEB与配体的结合，SEB也阻断这两种抗体的相互作用，表明结合位点具有高度选择性。抗Id在十二指肠用SEB激发时完全保护免受催吐反应和腹泻，并抑制皮肤速发型反应。此外，抗Id作为拮抗剂本身不触发生物学功能。这表明抗Id是预防细菌毒素诱导的肠道紊乱的有用工具。
