Identification of three immunodominant motifs with atypical isotype profile scattered over the Onchocerca volvulus proteome.
Identification of three immunodominant motifs with atypical isotype profile scattered over the Onchocerca volvulus proteome.
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DOI：
10.1371/journal.pntd.0005330
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发表时间：
2017-01
影响因子：
3.8
通讯作者：
Stuyver LJ
中科院分区：
文献类型：
--
作者：
Lagatie O;Van Dorst B;Stuyver LJ
了解丝虫线虫盘尾丝虫感染后的免疫反应以及这种寄生虫为了逃避免疫介导的消除而进化的机制对于扩展可用于诊断、治疗和疫苗开发的工具箱至关重要。使用高密度肽微阵列，我们扫描了喀麦隆盘尾丝虫病患者和来自南部非洲的健康对照的整个蛋白质组线性表位库，从而鉴定了 249 种免疫显性抗原肽。基序分析发现，3 个免疫显性基序（包含 3 个线性表位）分别存在于这些肽中的 70 个、43 个和 31 个中，并且似乎分散在看似不相关的蛋白质中的整个蛋白质组中。这些线性表位显示出具有以 IgG1、IgG3、IgE 和 IgM 为主的非典型同种型特征，这与慢性活动性蠕虫感染中常见的 IgG4 反应形成对比。这些线性表位基序的鉴定可能会导致新的诊断开发，但需要进一步评估针对常见共感染人类线虫感染的交叉反应性。丝虫寄生虫盘尾丝虫感染是河盲症的原因。我们分析了感染个体针对这种寄生虫的免疫反应，以确定线性表位。使用高密度肽微阵列，我们在盘尾丝虫蛋白质组中发现了三个免疫显性基序，可诱导广泛的 IgG 反应，但不存在针对寄生虫的典型 IgG4 免疫反应。我们的研究确定了新的潜在表位序列，可用于检测盘尾丝虫感染。
Understanding the immune response upon infection with the filarial nematode Onchocerca volvulus and the mechanisms that evolved in this parasite to evade immune mediated elimination is essential to expand the toolbox available for diagnostics, therapeutics and vaccines development. Using high-density peptide microarrays we scanned the proteome-wide linear epitope repertoire in Cameroonian onchocerciasis patients and healthy controls from Southern Africa which led to the identification of 249 immunodominant antigenic peptides. Motif analysis learned that 3 immunodominant motifs, encompassing 3 linear epitopes, are present in 70, 43, and 31 of these peptides, respectively and appear to be scattered over the entire proteome in seemingly non-related proteins. These linear epitopes are shown to have an atypical isotype profile dominated by IgG1, IgG3, IgE and IgM, in contrast to the commonly observed IgG4 response in chronic active helminth infections. The identification of these linear epitope motifs may lead to novel diagnostic development but further evaluation of cross-reactivity against common co-infecting human nematode infections will be needed. Infection with the filarial parasite Onchocerca volvulus is the cause of river blindness. We analyzed the immune response against this parasite in infected individuals in order to identify linear epitopes. Using high-density peptide microarrays we discovered three immunodominant motifs in the Onchocerca volvulus proteome that induce a broad IgG response, but the typical IgG4 immune response against parasites was absent. Our study led to the identification of novel potential epitope sequences that can potentially be used for detection of infection with Onchocerca volvulus.