Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenges.
Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenges.
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DOI：
10.1371/journal.ppat.1002041
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发表时间：
2011-05
期刊：
影响因子：
6.7
通讯作者：
Hanke T
中科院分区：
文献类型：
--
作者：
Im EJ;Hong JP;Roshorm Y;Bridgeman A;Létourneau S;Liljeström P;Potash MJ;Volsky DJ;McMichael AJ;Hanke T
T细胞对病毒等复杂抗原的免疫优势仍不完全清楚。一些数据表明，对病毒的显性反应不一定是最具保护性的，而另一些数据则暗示，显性反应是最重要的。这个问题对疫苗的合理设计相当重要，特别是对人类免疫缺陷病毒1型和丙型肝炎病毒等变量逃逸病毒的疫苗。在这里，我们展示了优势表位的顺序失活高于剩余的次要决定因素。重要的是，我们证明了，如果在疫苗接种方案中至少允许一次亚优势表位局部或暂时主导T细胞诱导，就可以诱导强大的反应并保护整个病毒。因此，将T细胞免疫反应从自然病毒感染过程中识别的高度可变的决定因素重新集中到次优势但保守的区域是可能的，值得在人类身上进行评估。人体对感染的反应主要是集中在少数蛋白质区域的强烈免疫反应，而忽略了其他区域。这些强烈的反应可能对不变的病毒具有保护作用，但无法控制快速变化的病毒。特别是对于艾滋病病毒，在自然感染期间，少数靶区是高度可变的，并且迅速变化，不被安装的反应，即逃逸识别。在这里，我们证明了即使是自然识别不足的蛋白质区域也可以诱导强大的反应并提供对整个病毒的保护，因此应该通过疫苗接种策略来利用。
Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans. The body's reaction to infections is dominated by strong immune responses focused on a small number of protein regions, while ignoring the other. These strong responses may be protective against invariant viruses, but fail to control viruses that can change quickly. In particular for the AIDS virus, it happens that the few targeted regions during natural infection are highly variable, and rapidly change and become unrecognized by the mounted responses, i.e. escape. Here, we demonstrated that even the naturally under-recognized protein regions can induce robust responses and confer protection against whole viruses, and therefore should be made use of by vaccination strategies.
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5.5
作者：
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