Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action

Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action
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产肠毒素大肠杆菌肠毒素突变体A亚基的低毒性与其强佐剂作用的关系

DOI:
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发表时间:
1997
期刊:
影响因子:
6.4
通讯作者:
Y. AsANot
Y. AsANot
中科院分区:
医学2区
文献类型:
--
作者:
T. Tsuji;T. Yokochi;H. Kamiya;Y. Kawamoto;A. Miyama;Y. AsANot

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在此描述的工作中,确定了大肠杆菌肠毒素 A 亚基 Arg192 或附近残基中的无切口是否以及如何影响毒素的生物活性。通过删除对毒性至关重要的三肽 Arg192-Thr193-Ile194,构建了突变毒素,使其缺乏 A 亚基中的切口位点。在存在或不存在 ADP-核糖基化因子的情况下,突变毒素均不表现出胍丁胺 ADP-核糖基转移酶活性,并且与 LT 相比,其腹泻活性较低,环 AMP 诱导较低。与LT相比,突变毒素对麻疹病毒、匙孔跛行血蓝蛋白、牛免疫球蛋白和卵清蛋白的抗体反应表现出更强的佐剂作用。突变毒素毒性的改变可能与抗体对抗原反应的有效佐剂作用密切相关。讨论了两项活动之间的关系。
In the work described here it was determined if and how unnicking in the A subunit of Escherichia coli enterotoxin at Arg192 or nearby residues affected biological activities of the toxin. The mutant toxin was constructed to lack the nick site in the A subunit by deleting the tripeptide Arg192‐Thr193‐Ile194, which is essential for toxicity. The mutant toxin did not exhibit agmatine ADP‐ribosyltransferase activity in the presence or absence of the ADP‐ribosylation factor and had less diarrhoeal activity and lower induction of cyclic AMP than did LT. The mutant toxin exhibited a much stronger adjuvant action on antibody responses to measles virus, keyhole limpt haemocyanin, bovine immunoglobulin and ovalbumin compared with LT. The altered toxicity of the mutant toxin might be closely related to the potent adjuvant action on antibody responses to antigens. The relationship between two activities is discussed.