A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells
A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells
复制标题
DOI：
10.1016/j.immuni.2012.11.021
复制
发表时间：
2013-03-21
期刊：
影响因子：
32.4
通讯作者：
Appay, Victor
中科院分区：
文献类型：
--
作者：
Ladell, Kristin;Hashimoto, Masao;Appay, Victor
免疫系统适应快速进化病毒的能力是有效免疫的主要特征，但其分子基础尚不清楚。在此，我们研究了针对由人白细胞抗原（HLA）-B*2705呈递的免疫显性p24 GAG衍生表位KK 10（KRWIILGLNK（263-272））的HIV-1特异性CD 8（+）T细胞保护性应答。我们发现，交叉反应性CD 8（+）T细胞克隆型被动员起来，以对抗可以直接影响T细胞受体（TCR）识别的HIV-1变体的快速出现。这些新招募的克隆型表达的TCR以相似的亲和力和几乎相同的对接模式与野生型和突变型KK 10抗原接合，从而解释了它们在HLA-B*2705（+）个体中的抗病毒功效。因此，保护性CD 8（+）T细胞库包括控制TCR可及突变的能力，最终驱动破坏抗原呈递的更复杂的病毒逃逸变体的发展。
The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8(+) T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK(263-272)) presented by human leukocyte antigen (HLA)-B*2705. We found that cross-reactive CD8(+) T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B*2705(+) individuals. A protective CD8(+) T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.