Absence of viral escape within a frequently recognized HLA-A26-restricted CD8+ T-cell epitope targeting the functionally constrained hepatitis C virus NS5A/5B cleavage site.
Absence of viral escape within a frequently recognized HLA-A26-restricted CD8+ T-cell epitope targeting the functionally constrained hepatitis C virus NS5A/5B cleavage site.
复制标题
在针对功能受限的丙型肝炎病毒 NS5A/5B 裂解位点的常见 HLA-A26 限制性 CD8 T 细胞表位内不存在病毒逃逸。
DOI：
--
复制
发表时间：
2007
影响因子：
3.8
通讯作者：
R. Thimme
中科院分区：
文献类型：
--
作者：
C. Neumann;Thomas A. Killinger;J. Timm;S. Southwood;D. McKinney;H. Blum;R. Thimme
CD8(+)T细胞反应是丙型肝炎病毒(HCV)感染的核心，病毒逃避这些CD8(+)T细胞反应被认为是丙型肝炎病毒持续存在的主要原因。然而，决定CD8逃逸突变出现的因素还不是很清楚。本文首次报道了四个人类白细胞抗原A26限制性CD8(+)T细胞表位的鉴定。值得注意的是，这四个表位中有两个位于NS3/4A和NS5A/5B裂解位点。后一种表位针对所有(3/3)急性、缓解型丙型肝炎病毒感染的患者，以及相对较高比例(4/14)的慢性丙型肝炎病毒感染患者。重要的是，与NS5A/5B裂解位点相对应的表位的特征是完全没有序列变异，尽管在我们的队列中存在功能性的病毒特异性CD8(+)T细胞。这些结果支持了先前的发现，即该区域内存在明确的功能限制。他们还提出，病毒逃逸的缺乏可能是由病毒适应成本决定的，并突出了免疫疗法的一个有吸引力的靶点。
CD8(+) T-cell responses are central for the resolution of hepatitis C virus (HCV) infection, and viral escape from these CD8(+) T-cell responses has been suggested to play a major role in HCV persistence. However, the factors determining the emergence of CD8 escape mutations are not well understood. Here, the first identification of four HLA-A26-restricted CD8(+) T-cell epitopes is reported. Of note, two of these four epitopes are located in the NS3/4A and NS5A/5B cleavage sites. The latter epitope is targeted in all (three of three) patients with acute, resolving HCV infection and in a relatively high proportion (four of 14) of patients with chronic HCV infection. Importantly, the epitope corresponding to the NS5A/5B cleavage site is characterized by the complete absence of sequence variations, despite the presence of functional virus-specific CD8(+) T cells in our cohort. These results support previous findings that showed defined functional constraints within this region. They also suggest that the absence of viral escape may be determined by viral fitness cost and highlight an attractive target for immunotherapies.
影响因子：
32.4
作者：
Erickson, AL;Kimura, Y;Walker, CM
通讯作者：
Walker, CM
影响因子：
29.4
作者：
Lauer, GM;Barnes, E;Klenerman, P
通讯作者：
Klenerman, P