Coxsackievirus group B (CVB) contains six serotypes that can affect various organs. Some of these organ-specific diseases such as myocarditis and pancreatitis can be caused by more than one serotype. Thus, development of immunological tools common to multiple serotypes is desired. This is especially critical for analyzing antigen-specific T cell responses at a single cell level. To this end, we made efforts to identify the immunogenic epitopes of CVB3 leading us to localize three T cell epitopes within the viral protein 1 (VP1) namely, VP1 681-700, VP1 721-740 and VP1 771-790. First, we confirmed their immunogenicity in the immunization settings. Second, we sought to verify the ability of VP1 epitopes to bind major histocompatibility complex (MHC) class II (IAk) molecules. Third, we created MHC class II (IAk) dextramers and tetramers and ascertained the T cell responses to be antigen-specific. Fourth, we analyzed the T cell responses in animals infected with CVB3 and noted the magnitude of antigen-specific T cell responses occurring in the order of VP1 721-740 and VP1 681-700 followed by VP1 771-790 as verified by proliferation assay and IAk tetramer staining. All epitopes induced interferon (IFN)-γ as a major cytokine. Finally, we investigated whether the VP1 tools generated for CVB3 can also be used to verify T cell responses in infections caused by other serotypes. To this end, we established the CVB4 infection model in A/J mice and found that the CVB4 infection led to the induction of IFN-γ-producing T cell responses primarily for VP1 721-740 and VP1 681-700. Thus, the VP1-specific tools, particularly IAk tetramers can be used to monitor anti-viral T cell responses in multiple CVB serotypes.

中文翻译：

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免疫原性抗原决定簇的确定，该抗原决定簇可以检测多种血清型的B组柯萨奇病毒感染的抗原特异性T细胞反应。

柯萨奇病毒B组（CVB）包含六种血清型，可以影响各个器官。这些器官特异性疾病中的一些，例如心肌炎和胰腺炎，可能是由一种以上的血清型引起的。因此，需要开发多种血清型共有的免疫学工具。这对于在单个细胞水平上分析抗原特异性T细胞反应特别重要。为此，我们努力鉴定CVB3的免疫原性表位，从而使我们在病毒蛋白1（VP1）中定位了三个T细胞表位，即VP1 681-700，VP1 721-740和VP1 771-790。首先，我们在免疫设置中确认了它们的免疫原性。第二，我们试图验证VP1表位结合主要组织相容性复合体（MHC）II类（IAk）分子的能力。第三，我们创建了MHC II类（IAk）右旋体和四聚体，并确定T细胞应答是抗原特异性的。第四，我们分析了受CVB3感染的动物的T细胞反应，并指出了抗原特异性T细胞反应的幅度，依次为VP1 721-740和VP1 681-700，随后是VP1 771-790，这已通过增殖测定和IAk四聚体染色。所有表位均将干扰素（IFN）-γ诱导为主要细胞因子。最后，我们调查了为CVB3生成的VP1工具是否还可以用于验证其他血清型引起的感染中的T细胞反应。为此，我们在A / J小鼠中建立了CVB4感染模型，发现CVB4感染导致主要针对VP1 721-740和VP1 681-700的产生IFN-γ的T细胞反应的诱导。因此，VP1专用工具