Recognition of variant rifin antigens by human antibodies induced during natural Plasmodium falciparum infections

Recognition of variant rifin antigens by human antibodies induced during natural Plasmodium falciparum infections
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DOI:
10.1128/iai.70.12.7013-7021.2002
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发表时间:
2002-12-01
影响因子:
3.1
通讯作者:
Klinkert, MQ
Klinkert, MQ
中科院分区:
医学2区
文献类型:
--
作者:
Abdel-Latif, MS;Khattab, A;Klinkert, MQ

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已知来自疟疾流行地区的个体的抗体与寄生虫衍生的红细胞表面蛋白反应。迄今为止描述的主要免疫原性和克隆变体表面抗原是恶性疟原虫红细胞膜蛋白1(PfEMP-1),其由多拷贝var基因家族的成员编码。我们在这里报告,rifin蛋白(RIF蛋白),属于最大的已知家庭的可变感染的红细胞表面表达的蛋白质,也是天然免疫原性。重组RIF蛋白用于分析生活在疟疾传播密集地区的个体的抗体应答。在大多数接受检测的成年人中检测到抗rifin抗体水平升高,而在疟疾暴露儿童中这种抗体的流行率要低得多。尽管rif序列和高基因拷贝数之间存在高度多样性,但恶性疟原虫感染似乎可以诱导与给定社区中许多寄生虫分离株中的几种变体rifin分子交叉反应的抗体,并且免疫应答在高流行地区最有可能随时间推移而稳定。通过荧光显微镜将该蛋白定位在环状和年轻滋养体感染的红细胞的膜上,所述红细胞具有来自具有重组RIF蛋白特异性的人免疫血清的抗体。
Antibodies from individuals living in areas where malaria is endemic are known to react with parasite-derived erythrocyte surface proteins. The major immunogenic and clonally variant surface antigen described to date is Plasmodium-falciparum erythrocyte membrane protein 1 (PfEMP-1), which is encoded by members of the multicopy var gene family. We report here that rifin proteins (RIF proteins), belonging to the largest known family of variable infected erythrocyte surface-expressed proteins, are also naturally immunogenic. Recombinant RIF proteins were used to analyze the antibody responses of individuals living in an area of intense malaria transmission. Elevated anti-rifin antibody levels were detected in the majority of the adult population tested, whereas the prevalence of such antibodies was much lower in malaria-exposed children. Despite the high degree of diversity between rif sequences and the high gene copy number, it appears that P. falciparum infections can induce antibodies that cross-react with several variant rifin molecules in many parasite isolates in a given community, and the immune response is most likely to be stable over time in a hyperendemic area. The protein was localized by fluorescence microscopy on the membrane of ring and young trophozoite-infected erythrocytes with antibodies from human immune sera with specificities for recombinant RIF protein.