Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses
Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses
复制标题
DOI：
10.1128/jvi.79.7.4329-4339.2005
复制
发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Doherty, PC
中科院分区：
文献类型：
--
作者：
Andreansky, SS;Stambas, J;Doherty, PC
利用经反向遗传学修饰的H1N1和H3N2型流感病毒，研究了针对其他抗原的CD8(+)T细胞在多大程度上扩展以补偿显著的(DNP366)-N-b和D(B)PA(224)表位的突变损失。经支气管肺泡灌洗后，小鼠的脾和炎症组织中CD8(+)K(B)PB1(703)(+)、CD8(+)K(B)NS2(114)(+)和CD8(+)D(B)PB1-F2(62)(+)T细胞数量显著增加。当这种质数-助推方案被颠倒时，效果就不那么一致了。此外，尽管细胞因子染色测量的反应质量显示出一些证据表明，当这些次要的CD8(+)-T细胞群体被迫发挥更突出的作用时，反应质量发生了改变，但影响相对较小，没有出现一致的模式。二次攻击后克隆扩增增强的幅度表明，用-NP-PA病毒进行的初始增强总体上与暴露于未处理病毒后的反应幅度几乎不同。当用感染病毒的细胞作为刺激物的ELISPOT分析测量总反应时，确实证明了这一点。更令人惊讶的是，尽管对CD8(+)(KPB703+)-P-b、CD8(+)K(B)NS2(114)(+)和CD8(+)D(B)PB1-F2(62)(+)集合的单独分析没有显示代偿性扩张，但在初级挑战之后也看到了同样的效果。一种可能的解释是，在初次接触-NP-PA缺失病毒后，出现了新的、迄今尚未检测到的表位。这些发现对自然感染和疫苗都有影响。
The extent to which CD8(+) T cells specific for other antigens expand to compensate for the mutational loss of the prominent (DNP366)-N-b and D(b)PA(224) epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8(+) K(b)PB1(703)(+), CD8(+) K(b)NS2(114)(+), and CD8(+) D(b)PB1-F2(62)(+) T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the -NP-PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8(+)-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the -NP-PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8(+) (KPB703+)-P-b, CD8(+) K(b)NS2(114)(+), and CD8(+) D(b)PB1-F2(62)(+) sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the -NP-PA deletion viruses. These findings have implications for both natural infections and vaccines.