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克氏锥虫 TcI 抗原的糖基化揭示了其被恰加斯血清识别。

Glycosylation of Trypanosoma cruzi TcI antigen reveals recognition by chagasic sera.

机构信息

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Centre for Molecular Processing, School of Biosciences, University of Kent, Canterbury, Kent, UK.

出版信息

Sci Rep. 2020 Oct 2;10(1):16395. doi: 10.1038/s41598-020-73390-9.

Abstract

Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.

摘要

恰加斯病被认为是拉丁美洲最重要的寄生虫病。原生动物病原体克氏锥虫由六个遗传谱系 TcI-TcVI 组成。由于克氏锥虫在宿主组织中的隔离和复制,对与心肌病和胃肠道病理严重程度相关的谱系进行基因分型受到阻碍。我们基于在真核生物利什曼原虫 Tarentolae 中表达重组锥虫小表面抗原(gTSSA-I),描述了针对 TcI(亚马逊河以北主要谱系)的血清学特异性,以允许抗原的真实糖基化和结构。来自 TcI 流行地区的血清识别 gTSSA-I(74/146;50.7%),与 gTSSA-II/V/VI 重组抗原的常见成分无交叉反应。抗原性通过 gTSSA-I 糖基化的化学(过碘酸盐)氧化而被消除,但在构象热变性后保留。相反,非流行疟疾血清中非特异性识别 gTSSA-I 被热变性消除。TcI 特异性血清学有助于研究谱系与不同临床表现之间的关系。在寻找免疫原性抗原时,糖基化不容忽视。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d4/7532467/ad9eedb1130a/41598_2020_73390_Fig1_HTML.jpg

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