Uneven distribution of MHC class II epitopes within the influenza virus
Uneven distribution of MHC class II epitopes within the influenza virus
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DOI：
10.1016/j.vaccine.2005.07.096
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发表时间：
2006-01-23
期刊：
影响因子：
5.5
通讯作者：
Woodland, DL
中科院分区：
文献类型：
--
作者：
Crowe, SR;Miller, SC;Woodland, DL
T 细胞表位的鉴定对于理解感染过程中宿主的免疫反应至关重要。虽然人们对 C57BL/6 小鼠流感病毒感染后的 MHC I 类限制性反应了解很多，迄今为止已鉴定出超过 16 个 CD8 表位，但对 MHC II 类限制性反应知之甚少。目前，仅鉴定了少数 I-A(b) 限制性 T 辅助表位。因此，关于该系统中存在多少 II 类表位以及这些表位是否均匀分布在最丰富的病毒蛋白中，仍然存在几个重要的问题。为了解决这些问题，我们分析了 C57BL/6 (H-2(b)) 小鼠中驱动 CD4(+) T 细胞对流感病毒感染作出反应的表位库。使用来自每种病毒蛋白的一组重叠肽，我们发现大约 20-30 个表位驱动 CD4(+) T 细胞反应，并且这些肽中的大多数源自 NP 和 HA 蛋白。我们还能够证明，接种新鉴定的表位之一 HA(211-225)/A(b) 会导致流感病毒攻击后表位特异性 T 细胞数量增加，病毒滴度显着降低。 (c) 2005 Elsevier Ltd. 保留所有权利。
The identification of T cell epitopes is crucial for the understanding of the host immune response during infection. While much is known about the MHC class I-restricted response following influenza virus infection of C57BL/6 mice, with over 16 CD8 epitopes identified to date, less is known about the MHC class II-restricted response. Currently, only a few I-A(b)-restricted T helper epitopes have been identified. Therefore, several important questions remain about how many class II epitopes exist in this system and whether these epitopes are evenly distributed within the most abundant viral proteins. In order to address these questions, we analyzed the repertoire of epitopes that drive the CD4(+) T cell response to influenza virus infection in C57BL/6 (H-2(b)) mice. Using a panel of overlapping peptides from each of the viral proteins we show that approximately 20-30 epitopes drive the CD4(+) T cell response and that the majority of these peptides are derived from the NP and HA proteins. We were also able to demonstrate that vaccination with one of the newly identified epitopes, HA(211-225)/A(b), resulted in increased epitope-specific T cell numbers and a significant reduction in viral titers following influenza virus challenge. (c) 2005 Elsevier Ltd. All rights reserved.