Vertical T cell immunodominance and epitope entropy determine HIV-1 escape
Vertical T cell immunodominance and epitope entropy determine HIV-1 escape
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DOI：
10.1172/jci65330
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发表时间：
2013-01-01
影响因子：
15.9
通讯作者：
Goonetilleke, Nilu
中科院分区：
文献类型：
--
作者：
Liu, Michael K. P.;Hawkins, Natalie;Goonetilleke, Nilu
HIV-1在反应性表位中及其周围积累突变，以逃避CD 8（+）T细胞的识别和杀伤。因此，HIV-1逃逸时间的测量应该提供关于哪些参数对于T细胞介导的HIV-1体内控制最重要的信息。主要的HIV-1特异性T细胞反应在17个个体中被完全绘制，并且针对每个表位测量病毒逃逸的时间，其范围从几天到几年不等。虽然个体T细胞反应的幅度更高与更快速的逃逸相关，但最重要的T细胞测量是在急性感染中测量的相对免疫优势。这表明受试者水平或“垂直”免疫优势是HIV-1感染中体内CD 8（+）T细胞压力的主要决定因素。相反，逃逸被靶向表位的较低群体变异性或熵显著减慢。免疫优势和表位熵结合起来解释了逃逸时间的一半变化。这些数据解释了CD 8（+）T细胞如何在逃逸非常缓慢的情况下施加显著和持续的HIV-1压力，并且在个体内，其他T细胞因子对HIV-1逃逸的影响应在免疫优势的背景下考虑。
HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8(+) T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell-mediated in vivo control of HIV-1. Primary HIV-1 specific T cell responses were fully mapped in 17 individuals, and the time to virus escape, which ranged from days to years, was measured for each epitope. While higher magnitude of an individual T cell response was associated with more rapid escape, the most significant T cell measure was its relative immunodominance measured in acute infection. This identified subject-level or "vertical" immunodominance as the primary determinant of in vivo CD8(+) T cell pressure in HIV-1 infection. Conversely, escape was slowed significantly by lower population variability, or entropy, of the epitope targeted. Immunodominance and epitope entropy combined to explain half of all the variability in time to escape. These data explain how CD8(+) T cells can exert significant and sustained HIV-1 pressure even when escape is very slow and that within an individual, the impacts of other T cell factors on HIV-1 escape should be considered in the context of immunodominance.