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抗小鼠巨细胞病毒中和单克隆抗体的特性分析

Characterization of neutralizing monoclonal antibodies to murine cytomegalovirus.

作者信息

Farrell H E, Shellam G R

机构信息

Department of Microbiology, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.

出版信息

J Gen Virol. 1990 Mar;71 ( Pt 3):655-64. doi: 10.1099/0022-1317-71-3-655.

DOI:10.1099/0022-1317-71-3-655
PMID:2155998
Abstract

Monoclonal antibodies (MAbs) and polyclonal antibodies raised in mice to murine cytomegalovirus (MCMV) were characterized in vitro by their virus-neutralizing activity and their reactivity with MCMV polypeptides and MCMV-infected mouse embryo fibroblasts (MEF). MCMV was neutralized by the MAbs prior to virus adsorption to MEF by a complement-dependent mechanism. Although the neutralization of MCMV prior to virus adsorption to MEF by polyclonal antibodies was enhanced in the presence of complement, MCMV was also neutralized by a complement-independent mechanism after virus adsorption. No correlation was observed between the level of neutralization of MCMV and the ability of MAbs or polyclonal antibodies to interfere with the binding of the virus to MEF. As the neutralization of MCMV with polyclonal antibodies by both complement-dependent and -independent mechanisms may reflect the interaction of antibodies with different specificities, the ability of each MAb to interact with a second MAb was investigated. One MAb, 1E8, inhibited the neutralizing activity of several other MAbs. Several MAbs reacted with multiple polypeptides by immunoprecipitation and Western blotting analysis; MAb AC1 cross-reacted with a neutralizing 92K/98K MCMV domain and a 70K ribonucleoprotein, the latter with which sera from patients with connective tissue diseases also reacted. This suggests that an homology exists between these proteins, which may lead to the development of autoimmune manifestations in vivo.

摘要

针对鼠巨细胞病毒(MCMV)在小鼠体内产生的单克隆抗体(MAb)和多克隆抗体,在体外通过其病毒中和活性、与MCMV多肽及MCMV感染的小鼠胚胎成纤维细胞(MEF)的反应性进行了表征。在病毒吸附到MEF之前,MAb通过补体依赖机制中和MCMV。虽然在补体存在的情况下,多克隆抗体在病毒吸附到MEF之前对MCMV的中和作用增强,但在病毒吸附后,MCMV也通过补体非依赖机制被中和。未观察到MCMV的中和水平与MAb或多克隆抗体干扰病毒与MEF结合能力之间的相关性。由于多克隆抗体通过补体依赖和非依赖机制对MCMV的中和作用可能反映了具有不同特异性的抗体之间的相互作用,因此研究了每种MAb与另一种MAb相互作用的能力。一种MAb,即1E8,抑制了其他几种MAb的中和活性。通过免疫沉淀和蛋白质印迹分析,几种MAb与多种多肽发生反应;MAb AC1与一个具有中和作用的92K/98K MCMV结构域和一个70K核糖核蛋白发生交叉反应,结缔组织病患者的血清也与后者发生反应。这表明这些蛋白质之间存在同源性,这可能导致体内自身免疫表现的发生。

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