CD4+ Th immunogenicity of the Ascaris spp. secreted products
CD4+ Th immunogenicity of the Ascaris spp. secreted products
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DOI：
10.1038/s41541-020-0171-z
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发表时间：
2020-03-20
期刊：
影响因子：
9.2
通讯作者：
Alvaro-Benito, Miguel
中科院分区：
文献类型：
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作者：
Ebner, Friederike;Morrison, Eliot;Alvaro-Benito, Miguel
蛔虫属是人类和动物的主要健康问题，并且需要了解其抗原的免疫原性以开发迫切需要的疫苗。寄生虫分泌的产物代表蛔虫属的最相关但复杂的（>250种蛋白质）抗原。定义了病原体与宿主的相互作用我们应用体外抗原处理系统结合定量蛋白质组学来鉴定蛔虫分泌产物中潜在的CD 4（+）T-h细胞表位。这种方法大大限制了使用常规CD 4（+）T-h细胞表位预测工具的表位的理论列表。我们证明了我们的方法的特异性和实用性的两组候选人名单，使我们能够识别命中排除一个或两个计算方法。更重要的是，通过实验确定的候选者之一清楚地证明了健康人类个体中存在针对这些抗原的病原体反应性T细胞。因此，我们的工作管道鉴定了针对蛔虫属的第一个人T细胞表位。并且代表了用于表征复合抗原，特别是那些不易于进行体内实验验证的病原体的易于适应的平台。
Ascaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet complex (>250 proteins) antigens of Ascaris spp. as defining the pathogen-host interplay. We applied an in vitro antigen processing system coupled to quantitative proteomics to identify potential CD4(+) T-h cell epitopes in Ascaris-secreted products. This approach considerably restricts the theoretical list of epitopes using conventional CD4(+) T-h cell epitope prediction tools. We demonstrate the specificity and utility of our approach on two sets of candidate lists, allowing us identifying hits excluded by either one or both computational methods. More importantly, one of the candidates identified experimentally, clearly demonstrates the presence of pathogen-reactive T cells in healthy human individuals against these antigens. Thus, our work pipeline identifies the first human T cell epitope against Ascaris spp. and represents an easily adaptable platform for characterization of complex antigens, in particular for those pathogens that are not easily amenable for in vivo experimental validation.