Prolonged Antigen Presentation following an Acute Virus Infection Requires Direct and Then Cross-Presentation

Prolonged Antigen Presentation following an Acute Virus Infection Requires Direct and Then Cross-Presentation
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DOI:
10.4049/jimmunol.1302565
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发表时间:
2014-10-15
影响因子:
4.4
通讯作者:
Norbury, Christopher C.
Norbury, Christopher C.
中科院分区:
医学2区
文献类型:
--
作者:
Heipertz, Erica L.;Davies, Michael L.;Norbury, Christopher C.

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抗病毒CD8(+)T细胞识别专职APC表面的MHC I类肽复合物是许多潜在致命感染后有效免疫应答的必要步骤。尽管MHC I类肽的产生被认为与病毒的持续存在密切相关,但一些研究表明,在RNA病毒清除后,Ag呈递的持续性会持续很长一段时间。然而,负责病毒清除后的Ag呈递持续性的机制至今尚不清楚。在这项研究中,我们使用了一种重组DNA病毒表达不同形式的模型银研究机制延长银介绍在小鼠中。我们确定,Ag呈递的持久性包括三个不同的机制阶段,如下:正在进行的病毒复制,病毒感染细胞的持久性和Ag的交叉呈递。这些数据将允许操纵病毒载体中所含的Ag形式,以产生疫苗接种后产生的最有效和保护性的CD8(+)T细胞应答。
Antiviral CD8(+) T cell recognition of MHC class I-peptide complexes on the surface of professional APCs is a requisite step in an effective immune response following many potentially lethal infections. Although MHC class I-peptide production is thought to be closely linked to the continued presence of virus, several studies have shown that the persistence of Ag presentation occurs for an extended period of time following the clearance of RNA viruses. However, the mechanism responsible for Ag presentation persistence following viral clearance was unknown until now. In this study, we used a recombinant DNA virus expressing different forms of a model Ag to study the mechanism of prolonged Ag presentation in mice. We determined that the persistence of Ag presentation consists of three distinct mechanistic phases, as follows: ongoing viral replication, persistence of virally infected cells, and cross-presentation of Ag. These data will allow manipulation of the form of Ag contained within viral vectors to produce the most effective and protective CD8(+) T cell response to be generated following vaccination.