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在没有明确探针的情况下,如何在表达文库中选择恶性疟原虫的前体红细胞抗原。

How to select Plasmodium falciparum pre-erythrocytic antigens in an expression library without defined probe.

作者信息

Marchand C, Druilhe P

机构信息

Parasitologie Biomédicale, Institut Pasteur, Paris, France.

出版信息

Bull World Health Organ. 1990;68 Suppl(Suppl):158-64.

PMID:1709833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2393044/
Abstract

The restricted access to Plasmodium falciparum liver stages has greatly limited the analysis of the antigenic content of that stage. Due to the lack of material to perform immunochemical studies, of access to mRNA, and of monoclonal probes, we decided to screen a genomic library with stage-restricted human antibodies. This strategy led to the identification of a large number of DNA fragments encoding both sporozoite specific as well as liver-stage specific epitopes. Following the initial characterization of one liver-stage antigen, further screening was performed by using additional selective human antibodies. These were defined as having a high degree of reactivity with native antigens on either of the two stages while being negative with the already known molecules of the two stages. From this second screening and the study of cross-reactions, several subsets of DNA clones expressing antigens present on the surface of sporozoites, or in liver stages, or in both, could be identified. In exposed individuals a high prevalence of antibodies to several of these antigens was found.

摘要

对恶性疟原虫肝期的研究受限,这极大地限制了对该阶段抗原成分的分析。由于缺乏用于进行免疫化学研究的材料、获取mRNA的途径以及单克隆探针,我们决定用阶段特异性人抗体筛选基因组文库。这一策略导致鉴定出大量编码子孢子特异性和肝期特异性表位的DNA片段。在初步鉴定一种肝期抗原之后,使用额外的选择性人抗体进行了进一步筛选。这些抗体被定义为与两个阶段的天然抗原具有高度反应性,而与两个阶段已知分子呈阴性反应。通过第二次筛选和交叉反应研究,可以鉴定出几个表达存在于子孢子表面、肝期或两者中的抗原的DNA克隆亚群。在暴露个体中,发现针对其中几种抗原的抗体具有高流行率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/28ae913f3a13/bullwho00058-0165-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/32a850ca9b3b/bullwho00058-0161-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/19ef209f8e63/bullwho00058-0162-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/28ae913f3a13/bullwho00058-0165-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/32a850ca9b3b/bullwho00058-0161-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/19ef209f8e63/bullwho00058-0162-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c504/2393044/28ae913f3a13/bullwho00058-0165-a.jpg

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本文引用的文献

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Cultivation of the liver forms of Plasmodium vivax in human hepatocytes.间日疟原虫肝脏期在人肝细胞中的培养。
Nature. 1984;307(5949):367-9. doi: 10.1038/307367a0.
2
Species- and stage-specific antigens in exoerythrocytic stages of Plasmodium falciparum.
Am J Trop Med Hyg. 1984 May;33(3):336-41. doi: 10.4269/ajtmh.1984.33.336.
3
A liver-stage-specific antigen of Plasmodium falciparum characterized by gene cloning.一种通过基因克隆鉴定的恶性疟原虫肝期特异性抗原。
Nature. 1987;329(6135):164-7. doi: 10.1038/329164a0.
Front Microbiol. 2014 Nov 17;5:586. doi: 10.3389/fmicb.2014.00586. eCollection 2014.
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Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC).获得性针对间日疟原虫感染的抗体反应因趋化因子的达菲抗原受体(DARC)宿主基因型而异。
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5
The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas.疟疾病候选疫苗肝阶段抗原-3 在来自不同地理区域的恶性疟原虫分离株中高度保守。
Malar J. 2009 Oct 29;8:247. doi: 10.1186/1475-2875-8-247.
6
Human antibodies against Plasmodium falciparum liver-stage antigen 3 cross-react with Plasmodium yoelii preerythrocytic-stage epitopes and inhibit sporozoite invasion in vitro and in vivo.针对恶性疟原虫肝期抗原3的人源抗体与约氏疟原虫红细胞前期表位发生交叉反应,并在体外和体内抑制子孢子入侵。
Infect Immun. 2001 Jun;69(6):3845-52. doi: 10.1128/IAI.69.6.3845-3952.2001.
7
Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA types in the malaria vaccine candidate liver-stage antigen 3.疟疾疫苗候选肝期抗原3中针对HLA - B53及其他HLA类型的细胞毒性T淋巴细胞表位
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8
Immunogenicity of four Plasmodium falciparum preerythrocytic antigens in Aotus lemurinus monkeys.四种恶性疟原虫红细胞前期抗原在夜猴中的免疫原性
Infect Immun. 1998 Jul;66(7):3423-8. doi: 10.1128/IAI.66.7.3423-3428.1998.
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Evidence for diversity of Plasmodium falciparum sporozoite surface antigens derived from analysis of antibodies elicited in humans.通过分析人类体内诱导产生的抗体获得的关于恶性疟原虫子孢子表面抗原多样性的证据。
Infect Immun. 1990 Sep;58(9):2995-3001. doi: 10.1128/iai.58.9.2995-3001.1990.