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小鼠对日本血吸虫谷胱甘肽S-转移酶Sj26的反应。

Responses in mice to Sj26, a glutathione S-transferase of Schistosoma japonicum worms.

作者信息

Davern K M, Tiu W U, Morahan G, Wright M D, Garcia E G, Mitchell G F

机构信息

Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

出版信息

Immunol Cell Biol. 1987 Dec;65 ( Pt 6):473-82. doi: 10.1038/icb.1987.56.

Abstract

The genetic variation in antibody responses of mice to glutathione S-transferase (GST) enzymes of Schistosoma japonicum worms, and in particular to a Mr 26,000 species termed Sj26, was analysed. Sera from infected mice, or mice immunized with adjuvant and an Sj26 beta-galactosidase fusion protein produced in Escherichia coli (Sj26FP), or purified near-native recombinant Sj26 produced in E. coli (rSj26), were assayed by enzyme-linked immunosorbent assay (ELISA) for antibody titres to GST purified from adult worms. Anti-GST antibody levels are high in a mouse strain, WEHI 129/J, that is genetically resistant to infection with S. japonicum. Antibody responses to GST are low in BALB/c mice and intermediate in most other mouse strains analysed such as CBA/H and C57B1/6. Responsiveness to Sj26 in adjuvant is dominant in (BALB/c x WEHI 129/J)F1 hybrids. BALB/c.H-2b and BALB/c.H-2k mice are higher responders than BALB/c. One feature of antibody responses to Sj26 is the variability within a group of mice. When rSj26 conjugated to the hapten azobenzenearsonate was used as immunogen, BALB/c mice produced substantial amounts of anti-Sj26 antibodies. In an attempt to correlate antibody levels with resistance in infected mice, a new functional assay was devised to measure the ability of sera to inhibit the binding of rSj26 to glutathione. However, there was no correlation between inhibitory titre in this assay and the numbers of worms recovered. In regard to the candidacy of GST as a vaccinating antigen in schistosomiasis japonica, the data raise the problem of variable responsiveness to the antigen that will need to be overcome by antigen modification and/or powerful adjuvants.

摘要

分析了小鼠对日本血吸虫谷胱甘肽S-转移酶(GST)酶,特别是对一种称为Sj26的26000道尔顿分子量的抗体反应中的遗传变异。通过酶联免疫吸附测定(ELISA)检测感染小鼠、用佐剂和在大肠杆菌中产生的Sj26β-半乳糖苷酶融合蛋白(Sj26FP)免疫的小鼠或在大肠杆菌中产生的纯化的近天然重组Sj26(rSj26)的血清中针对从成虫纯化的GST的抗体滴度。在对日本血吸虫感染具有遗传抗性的小鼠品系WEHI 129/J中,抗GST抗体水平很高。在BALB/c小鼠中,对GST的抗体反应较低,而在大多数其他分析的小鼠品系如CBA/H和C57B1/6中则处于中等水平。在(BALB/c×WEHI 129/J)F1杂种中,对佐剂中Sj26的反应性占主导。BALB/c.H-2b和BALB/c.H-2k小鼠比BALB/c小鼠反应性更高。对Sj26的抗体反应的一个特点是一组小鼠内的变异性。当将与半抗原偶氮苯胂酸盐偶联的rSj26用作免疫原时,BALB/c小鼠产生了大量的抗Sj26抗体。为了将抗体水平与感染小鼠的抗性相关联,设计了一种新的功能测定法来测量血清抑制rSj26与谷胱甘肽结合的能力。然而,该测定法中的抑制滴度与回收的虫体数量之间没有相关性。关于GST作为日本血吸虫病疫苗接种抗原的候选资格,这些数据提出了对抗原反应性可变的问题,这需要通过抗原修饰和/或强效佐剂来克服。

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