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通过计算分析合理选择的表位可诱导小鼠T细胞增殖,并被曼氏血吸虫感染个体的血清识别。

Epitopes rationally selected through computational analyses induce T-cell proliferation in mice and are recognized by serum from individuals infected with Schistosoma mansoni.

作者信息

Lopes Marcelo D, Oliveira Flávio M, Coelho Ivan E V, Passos Maria J F, Alves Clarice C, Taranto Alex G, Júnior Moacyr C, Santos Luciana L, Fonseca Cristina T, Villar José A F P, Lopes Débora O

机构信息

Laboratório de Biologia Molecular, Universidade Federal de São João del-Rei, Rua Sebastião Gonçalves Coelho, Divinópolis, MG, Brasil.

Laboratório de Química Farmacêutica, Universidade Federal de São João del-Rei, Divinópolis, MG, Brasil.

出版信息

Biotechnol Prog. 2017 May;33(3):804-814. doi: 10.1002/btpr.2463. Epub 2017 Apr 16.

DOI:10.1002/btpr.2463
PMID:28371522
Abstract

Schistosomiasis is the second leading cause of death due to parasitic diseases in the world. Seeking an alternative for the control of disease, the World Health Organization funded the genome sequencing of the major species related to schistosomiasis to identify potential vaccines and therapeutic targets. Therefore, the aim of this work was to select T and B-cell epitopes from Schistosoma mansoni through computational analyses and evaluate the immunological potential of epitopes in vitro. Extracellular regions of membrane proteins from the Schistosoma mansoni were used to predict promiscuous epitopes with affinity to different human Major Histocompatibility Class II (MHCII) molecules by bioinformatics analysis. The three-dimensional structure of selected epitopes was constructed and used in molecular docking to verify the interaction with murine MHCII H2-IA . In this process, four epitopes were selected and synthesized to assess their ability to stimulate proliferation of CD4 T lymphocytes in mice splenocyte cultures. The results showed that Sm041370 and Sm168240 epitopes induced significant cell proliferation. Additionally, the four epitopes were used as antigens in the Indirect Enzyme-Linked Immunosorbent Assay (ELISA) to assess the recognition by serum from individuals infected with Schistosoma mansoni. Sm140560, Sm168240, and Sm041370 epitopes were recognized by infected individuals IgG antibodies. Therefore, Sm041370 and Sm168240 epitopes that stood out in in silico and in vitro analyses could be promising antigens in schistosomiasis vaccine development or diagnostic kits. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:804-814, 2017.

摘要

血吸虫病是全球因寄生虫病导致死亡的第二大主要原因。为寻求疾病控制的替代方法,世界卫生组织资助了与血吸虫病相关主要物种的基因组测序,以确定潜在的疫苗和治疗靶点。因此,本研究的目的是通过计算分析从曼氏血吸虫中筛选T细胞和B细胞表位,并在体外评估这些表位的免疫潜力。利用生物信息学分析,以曼氏血吸虫膜蛋白的细胞外区域预测与不同人类主要组织相容性复合体II类(MHCII)分子具有亲和力的多聚表位。构建所选表位的三维结构,并用于分子对接,以验证其与小鼠MHCII H2-IA的相互作用。在此过程中,筛选并合成了四个表位,以评估它们刺激小鼠脾细胞培养物中CD4 T淋巴细胞增殖的能力。结果显示,Sm041370和Sm168240表位可诱导显著的细胞增殖。此外,将这四个表位用作间接酶联免疫吸附测定(ELISA)中的抗原,以评估曼氏血吸虫感染个体血清的识别情况。Sm140560、Sm168240和Sm041370表位可被感染个体的IgG抗体识别。因此,在计算机模拟和体外分析中表现突出的Sm041370和Sm168240表位有望成为血吸虫病疫苗开发或诊断试剂盒中的抗原。© 2017美国化学工程师学会生物技术进展,33:804 - 814,2017年。

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