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来自疟疾流行地区的疟疾患者对恶性疟原虫红细胞膜蛋白1(PfEMP1)外显子2区域重组蛋白和合成肽的细胞和体液反应比较

Comparison of cellular and humoral responses to recombinant protein and synthetic peptides of exon2 region of Plasmodium falciparum erythrocyte membrane protein1 (PfEMP1) among malaria patients from an endemic region.

作者信息

Das Padmalaya, Grewal Jasvir S, Mahajan Babita, Chauhan Virander S

机构信息

Malaria Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, P. Box No. 10504, New Delhi - 110067, India.

出版信息

Parasitol Int. 2007 Mar;56(1):51-9. doi: 10.1016/j.parint.2006.11.003. Epub 2007 Jan 25.

Abstract

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of parasitized red blood cells (PRBCs) mediate adhesion of PRBCs to host vascular endothelial receptors and is considered responsible for pathogenesis of severe P. falciparum malaria. The present study was undertaken to measure cellular immune responses and serum antibody responses against recombinant exon2 protein, the most conserved region of PfEMP1, and its synthetic peptides. T cell recognizing this domain could provide universal help to B cells in recognizing variant epitopes located in the extracellular region of PfEMP1. Human peripheral blood mononuclear cells from malaria-exposed immune adults (IA), malaria patients with varying severity, and malaria unexposed healthy donors were stimulated with recombinant exon2 protein and six synthetic peptides from its sequence to estimate the proliferative, IFN-gamma, and IL-4 responses. Antibody responses against these synthetic peptides and exon2 protein were also studied. Positive proliferative, IFN-gamma, and IL-4 responses in IA group each were 60% with recombinant exon2 protein and 27-47% with different synthetic peptides. Antibody recognition was observed in 67% with exon2 and between 40 and 53% with different peptides. In malaria patients, frequency and magnitude of proliferative response, IL-4 concentration, and antibody recognition were far less than immune adults but IFN-gamma response was almost similar. Proportion of positive responders and the magnitude of response to synthetic peptides were low. Also, there was no consistency in response of different peptides towards proliferative, cytokine, and antibody responses in IA and malaria patient groups except for peptide 1. We presume peptide 1 is a potential vaccine candidate and different cocktails containing peptide 1 are being evaluated for their T cell immunogenicity.

摘要

恶性疟原虫红细胞膜蛋白1(PfEMP1)在被寄生红细胞(PRBCs)表面表达,介导PRBCs与宿主血管内皮受体的黏附,被认为是导致严重恶性疟原虫疟疾发病的原因。本研究旨在测量针对重组外显子2蛋白(PfEMP1最保守的区域)及其合成肽的细胞免疫反应和血清抗体反应。识别该结构域的T细胞可以在识别位于PfEMP1细胞外区域的变异表位方面为B细胞提供通用帮助。用重组外显子2蛋白及其序列中的六种合成肽刺激来自接触过疟疾的免疫成年人(IA)、不同严重程度的疟疾患者以及未接触过疟疾的健康供体的人外周血单个核细胞,以评估增殖反应、干扰素-γ和白细胞介素-4反应。还研究了针对这些合成肽和外显子2蛋白的抗体反应。IA组中,重组外显子2蛋白刺激后的阳性增殖反应、干扰素-γ反应和白细胞介素-4反应各为60%,不同合成肽刺激后的阳性反应为27%-47%。外显子2蛋白的抗体识别率为67%,不同肽的抗体识别率在40%-53%之间。在疟疾患者中,增殖反应的频率和幅度、白细胞介素-4浓度以及抗体识别率远低于免疫成年人,但干扰素-γ反应几乎相似。对合成肽的阳性反应者比例和反应幅度较低。此外,除肽1外,IA组和疟疾患者组中不同肽对增殖反应、细胞因子反应和抗体反应的反应没有一致性。我们推测肽1是一种潜在的疫苗候选物,目前正在评估含有肽1的不同组合的T细胞免疫原性。

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