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淋巴细胞性脉络丛脑膜炎病毒的蛋白质:病毒糖蛋白的抗原拓扑结构

Proteins of lymphocytic choriomeningitis virus: antigenic topography of the viral glycoproteins.

作者信息

Parekh B S, Buchmeier M J

出版信息

Virology. 1986 Sep;153(2):168-78. doi: 10.1016/0042-6822(86)90020-6.

DOI:10.1016/0042-6822(86)90020-6
PMID:2426862
Abstract

Topographical relationships among antigenic sites on the envelope glycoproteins of lymphocytic choriomeningitis virus (LCMV) were established using a panel of monoclonal antibodies (MAb) directed against viral GP-1 and GP-2. Purified MAb were radioiodinated and used as probes in a solid phase competitive binding assay. Epitopes on LCMV GP-1 were found to cluster in four antigenic sites. Five neutralizing MAb raised by immunization with the WE strain of LCMV reacted with a single topographic site, termed GP-1A, which was present on four strains of LCMV examined in this study. A second site, GP-1B, was characterized by two MAb which partially competed with one another and with a subset of neutralizing antibodies. This site appeared to be close to site A and was found to be nonneutralizing. The third site, GP-1C, contained sequential epitopes and was also nonneutralizing. Antibodies binding to site B enhanced the binding of MAb at site C, presumably through a conformational change. In addition to the common neutralizing site A, LCMV Armstrong strain (LCMV-Arm) GP-1 contained a second topographically related neutralizing site, GP-1D, which was specific for LCMV-Arm, absent in WE, and appeared to be the major immunogenic epitope on GP-1 of this virus. Analysis of MAb binding to LCMV GP-2 demonstrated the presence of three overlapping binding sites. GP-2A was defined by two antibodies while GP-2B and C represented binding sites of one antibody each. Guinea pigs primed with LCMV-Arm and challenged with LCMV-WE developed a significant immune response which was directed toward the common major neutralizing site, GP-1A, but had poor responses to the LCMV-Arm specific neutralizing site GP-1D. Immune sera contained antibody to site GP-1B but lacked detectable antibody to GP-1C.

摘要

利用一组针对淋巴细胞性脉络丛脑膜炎病毒(LCMV)包膜糖蛋白病毒糖蛋白1(GP-1)和病毒糖蛋白2(GP-2)的单克隆抗体(MAb),确定了LCMV包膜糖蛋白上抗原位点之间的拓扑关系。纯化的单克隆抗体经放射性碘化后,用作固相竞争结合试验中的探针。发现LCMV GP-1上的表位聚集在四个抗原位点。用LCMV的WE株免疫产生的五种中和单克隆抗体与一个单一的拓扑位点反应,该位点称为GP-1A,在本研究中检测的四种LCMV株中均存在。第二个位点GP-1B由两种单克隆抗体表征,它们彼此部分竞争,并与一部分中和抗体竞争。该位点似乎靠近位点A,且被发现无中和作用。第三个位点GP-1C包含连续表位,也无中和作用。与位点B结合的抗体可能通过构象变化增强了单克隆抗体在位点C的结合。除了常见的中和位点A外,LCMV阿姆斯特朗株(LCMV-Arm)的GP-1还包含第二个拓扑相关的中和位点GP-1D,该位点对LCMV-Arm具有特异性,在WE株中不存在,并且似乎是该病毒GP-1上的主要免疫原性表位。对单克隆抗体与LCMV GP-2结合的分析表明存在三个重叠的结合位点。GP-2A由两种抗体定义,而GP-2B和C分别代表一种抗体的结合位点。用LCMV-Arm免疫并用LCMV-WE攻击豚鼠,产生了显著的免疫反应,该反应针对常见的主要中和位点GP-1A,但对LCMV-Arm特异性中和位点GP-1D的反应较差。免疫血清含有针对位点GP-1B的抗体,但缺乏可检测到的针对GP-1C的抗体。

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