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.

虫属。这是人类和动物面临的主要健康问题，因此了解其抗原的免疫原性对于开发急需的疫苗是必需的。寄生虫分泌产品代表的最相关的，但复杂的（> 250种蛋白）抗原蛔虫属。定义病原体与宿主之间的相互作用。我们应用耦合到定量蛋白质组学来识别潜在的CD4的体外抗原处理系统⁺ Ť _ħ细胞表位在蛔虫-secreted产品。这种方法极大地限制了使用常规CD4 ⁺ T _h的表位的理论清单细胞表位预测工具。我们在两组候选者列表上展示了我们方法的特异性和实用性，使我们能够确定一种或两种计算方法所排除的匹配。更重要的是，通过实验确定的一种候选药物清楚地证明了健康人体内针对这些抗原的病原体反应性T细胞的存在。因此，我们的工作流程确定了第一个针对Ascaris spp的人类T细胞表位。代表了复杂抗原表征的容易适应的平台，特别是对于那些不易用于体内实验验证的病原体。