Direct presentation is sufficient for an efficient anti-viral CD8+ T cell response.

Direct presentation is sufficient for an efficient anti-viral CD8+ T cell response.
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DOI:
10.1371/journal.ppat.1000768
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发表时间:
2010-02-12
期刊:
影响因子:
6.7
通讯作者:
Sigal LJ
Sigal LJ
中科院分区:
医学1区
文献类型:
--
作者:
Xu RH;Remakus S;Ma X;Roscoe F;Sigal LJ

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直接呈递和交叉呈递(DP和CP)在多大程度上促进了CD8+ T细胞(TCD8+)对病毒的应答尚不清楚,主要是因为难以分离这两个过程。因此,虽然CP在DP的情况下已被清楚地证明,诱导的抗病毒TCD8+反应,排除CP从来没有被故意显示。使用牛痘病毒(VACV),这已被用作疫苗,以摆脱世界上的天花,并提出作为载体的许多其他疫苗,我们表明,DP是主要的机制,为引发的抗病毒TCD8+反应。这些发现为我们理解最有效的抗病毒疫苗之一如何诱导免疫力提供了重要的见解,并应有助于开发新型疫苗。专职抗原呈递细胞将病毒蛋白片段化,并将一些所得肽与细胞表面的MHC分子结合。当病毒特异性CD8+ T细胞识别这些病毒肽时,它们被激活,增殖并杀死病毒感染的细胞,以帮助清除体内的病毒。已经描述了由专职抗原呈递细胞呈递的肽的来源的两种途径。在交叉呈递中,抗原呈递细胞从其他细胞获得蛋白质,在病毒感染的情况下,这些细胞必须被感染。在直接呈递中,抗原呈递细胞自身合成蛋白质,因此,在对病毒的反应期间必须被感染。然而,直接呈递参与抗病毒反应从未被故意实验证明。在本文中,我们表明,直接呈递发生,是主要途径,以诱导CD8+ T细胞在感染牛痘病毒。这些发现为我们理解最有效的抗病毒疫苗之一如何诱导免疫力提供了重要的见解,并应有助于开发新型疫苗。
The extent to which direct- and cross-presentation (DP and CP) contribute to the priming of CD8+ T cell (TCD8+) responses to viruses is unclear mainly because of the difficulty in separating the two processes. Hence, while CP in the absence of DP has been clearly demonstrated, induction of an anti-viral TCD8+ response that excludes CP has never been purposely shown. Using vaccinia virus (VACV), which has been used as the vaccine to rid the world of smallpox and is proposed as a vector for many other vaccines, we show that DP is the main mechanism for the priming of an anti-viral TCD8+ response. These findings provide important insights to our understanding of how one of the most effective anti-viral vaccines induces immunity and should contribute to the development of novel vaccines. Professional antigen presenting cells fragment viral proteins and display some of the resulting peptides bound to MHC molecules at the cell surface. When virus-specific CD8+ T cells recognize these viral peptides they become activated, proliferate, and kill virus-infected cells to help rid the body of the virus. Two pathways have been described for the origin of the peptides presented by professional antigen presenting cells. In cross-presentation, the antigen presenting cells acquire the proteins from other cells which, in the case of a viral infection, must be infected. In direct presentation, the antigen presenting cells synthesize the proteins themselves and, therefore, during responses to viruses must be infected. However, the participation of direct presentation in anti-viral responses has never been deliberately demonstrated experimentally. In this paper we demonstrate that direct presentation occurs and is the main pathway to induce CD8+ T cells during infection with vaccinia virus. These findings provide important insights to our understanding of how one of the most effective anti-viral vaccines induces immunity and should contribute to the development of novel vaccines.
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