Reversal in the immunodominance hierarchy in secondary CD8+ T cell responses to influenza A virus:: Roles for cross-presentation and lysis-independent immunodomination
Reversal in the immunodominance hierarchy in secondary CD8+ T cell responses to influenza A virus:: Roles for cross-presentation and lysis-independent immunodomination
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DOI：
10.4049/jimmunol.173.8.5021
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Yewdell, JW
中科院分区：
文献类型：
--
作者：
Chen, W;Pang, K;Yewdell, JW
免疫优势是CD8(+)T细胞(TCD8+)对病原体、移植和肿瘤反应的中心特征。决定因素在免疫优势层次结构中占有稳定的位置(α、β等)。由响应TCD8+的频率定义。在本文中，我们研究了在小鼠的原发和继发性抗甲型流感病毒(IAV)反应中，α(酸性聚合酶(PA)(224-233))和β决定簇(核蛋白366-374)之间位置互换的机制。这种现象最近被认为与IAV感染的非树突状细胞(DC)不能产生PA(224-233)有关，并提出次级TCD8+主要由IAV感染的上皮细胞激活，而原代TCD8+主要由IAV感染的DC激活。在这项研究中，我们表明非DC不能产生PA(224-232)是相对的而不是绝对的，并且在二次抗IAV反应中优先使用交叉启动也可以解释修订的等级。我们进一步表明，核蛋白366-374特异性TCD8+对PA(224-233)特异性TCD8+的免疫支配在这一现象中发挥了关键作用，这不太可能是由APC或其他细胞的TCD8+裂解介导的。
Immunodominance is a central feature of CD8(+) T cell (TCD8+) responses to pathogens, transplants, and tumors. Determinants occupy a stable position in an immunodominance hierarchy (alpha-, beta-, etc.) defined by the frequencies of responding TCD8+. In this paper, we study the mechanistic basis for place-swapping between alpha-(acid polymerase (PA)(224-233)) and beta-determinants (nuclear protein 366-374) in primary vs secondary anti-influenza A virus (IAV) responses in mice. This phenomena was recently correlated with the inability of IAV-infected nondendritic cells (DCs) to generate PA(224-233), and it was proposed that secondary TCD8+ are principally activated by IAV-infected epithelial cells, while primary TCD8+ are activated by IAV-infected DCs. In this study, we show that the inability of non-DCs to generate PA(224-232) is relative rather than absolute, and that the preferential use of cross-priming in secondary anti-IAV responses can also account for the revised hierarchy. We further show that immunodomination of PA(224-233)-specific TCD8+ by nucleoprotein 366-374-specific TCD8+ plays a critical role in the phenomena, and that this is unlikely to be mediated by TCD8+ lysis of APCs or other cells.