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霍乱毒素、不耐热肠毒素I、不耐热肠毒素IIa和不耐热肠毒素IIb:神经节苷脂结合在I型和II型不耐热肠毒素免疫调节中的关键作用

Cholera toxin, LT-I, LT-IIa and LT-IIb: the critical role of ganglioside binding in immunomodulation by type I and type II heat-labile enterotoxins.

作者信息

Connell Terry D

机构信息

School of Medicine and Biomedical Sciences, Department of Microbiology and Immunology, 138 Farber Hall, 3435 Main St, Buffalo, NY 14214, USA.

出版信息

Expert Rev Vaccines. 2007 Oct;6(5):821-34. doi: 10.1586/14760584.6.5.821.

Abstract

The heat-labile enterotoxins expressed by Vibrio cholerae (cholera toxin) and Escherichia coli (LT-I, LT-IIa and LT-IIb) are potent systemic and mucosal adjuvants. Coadministration of the enterotoxins with a foreign antigen produces an augmented immune response to that antigen. Although each enterotoxin has potent adjuvant properties, the means by which the enterotoxins induce various immune responses are distinctive for each adjuvant. Various mutants have been engineered to dissect the functions of the enterotoxins required for their adjuvanticity. The capacity to strongly bind to one or more specific ganglioside receptors appears to drive the distinctive immunomodulatory properties associated with each enterotoxin. Mutant enterotoxins with ablated or altered ganglioside-binding affinities have been employed to investigate the role of gangliosides in enterotoxin-dependent immunomodulation.

摘要

霍乱弧菌表达的热不稳定肠毒素(霍乱毒素)以及大肠杆菌表达的热不稳定肠毒素(LT-I、LT-IIa和LT-IIb)是强效的全身和黏膜佐剂。将肠毒素与外来抗原共同给药可增强针对该抗原的免疫反应。尽管每种肠毒素都具有强大的佐剂特性,但每种佐剂诱导各种免疫反应的方式却各不相同。人们构建了各种突变体来剖析肠毒素发挥佐剂作用所需的功能。与一种或多种特定神经节苷脂受体的强结合能力似乎驱动了与每种肠毒素相关的独特免疫调节特性。具有缺失或改变的神经节苷脂结合亲和力的突变肠毒素已被用于研究神经节苷脂在肠毒素依赖性免疫调节中的作用。

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