Identification of a CD4 T cell epitope in the pneumonia virus of mice glycoprotein and characterization of its role in protective immunity
Identification of a CD4 T cell epitope in the pneumonia virus of mice glycoprotein and characterization of its role in protective immunity
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DOI：
10.1016/j.virol.2007.06.002
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发表时间：
2007-11-10
期刊：
影响因子：
3.7
通讯作者：
van der Most, Robbert G.
中科院分区：
文献类型：
--
作者：
Claassen, Erwin A. W.;van Bleek, Grada M.;van der Most, Robbert G.
小鼠肺炎病毒（PVM）会引起小鼠细支气管炎和肺炎。感染与肺部高水平的病毒复制有关，并导致肺部病毒特异性 CD8 T 细胞功能失活。由于其与严重的人类呼吸道合胞病毒 (RSV) 感染相似，小鼠 PVM 感染已被提议作为替代 RSV 模型。在这里，我们描述了 PVM 模型中保护性 T 细胞免疫的最低要求。使用来自 PVM 磷蛋白 P 的 CD8 T 细胞表位与卵清蛋白 (OVA) CD4 T 细胞表位相结合进行免疫，并没有赋予针对致命性 PVM 攻击的保护性免疫，这表明同源 CD4 T 细胞免疫可能发挥作用。为了确定 PVM 特异性 CD4 T 细胞反应的作用，我们使用一组重叠肽在糖蛋白 G 中绘制了 PVM CD4 T 细胞表位。尽管使用该表位进行免疫提供了一些保护，但仅在使用 PVM 特异性 CD4 和 CD8 T 细胞表位组合进行免疫后才观察到固体保护性免疫。对免疫小鼠中攻击后 T 细胞反应的分析表明，G 特异性肺 CD4 T 细胞表现出混合的 Th1/Th2 表型，其特征是在不存在明显病理学的情况下同时存在 IL-5 和 IFN-γ 分泌细胞。 (C) 2007 Elsevier Inc. 保留所有权利。
Pneumonia virus of mice (PVM) causes bronchiolitis and pneumonia in mice. Infection is associated with high levels of viral replication in the lungs and results in the functional inactivation of pulmonary virus-specific CD8 T cells. Due to its similarity to severe human respiratory syncytial virus (RSV) infection, PVM infection in mice has been proposed as an alternative RSV model. Here, we have delineated the minimal requirements for protective T cell immunity in the PVM model. Immunization with a CD8 T cell epitope from the PVM phosphoprotein P, combined with the ovalbumin (OVA) CD4 T cell epitope, did not confer protective immunity against lethal PVM challenge, suggesting a possible role of cognate CD4 T cell immunity. To determine the role of PVM-specific CD4 T cell responses, we mapped a PVM CD4 T cell epitope in the glycoprotein G, using a panel of overlapping peptides. Although immunization with this epitope provided some protection, solid protective immunity was only observed after immunization with a combination of the PVM-specific CD4 and CD8 T cell epitopes. Analysis of post-challenge T cell responses in immunized mice indicated that G-specific pulmonary CD4 T cells displayed a mixed Thl/Th2 phenotype, which was characterized by the presence of both IL-5 and IFN-gamma secreting cells, in the absence of overt pathology. (C) 2007 Elsevier Inc. All rights reserved.