Complex T-Cell Receptor Repertoire Dynamics Underlie the CD8+ T-Cell Response to HIV-1
Complex T-Cell Receptor Repertoire Dynamics Underlie the CD8+ T-Cell Response to HIV-1
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DOI：
10.1128/jvi.01765-14
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发表时间：
2015-01-01
影响因子：
5.4
通讯作者：
van Baarle, Debbie
中科院分区：
文献类型：
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作者：
Costa, Ana I.;Koning, Dan;van Baarle, Debbie
尽管CD8+T细胞对于体内HIV-1的控制很重要，但免疫功效的精确相关性仍不清楚。在这项研究中，我们对一组未接受过抗逆转录病毒治疗的长期感染 HIV-1 的个体的多个表位特异性的病毒序列变异和 T 细胞受体 (TCR) 库组成进行了全面分析。在抗原特异性TCR库多样性的变化和CD8+T细胞反应强度之间检测到负相关，反映了与同源病毒表位序列改变相关的克隆型扩张和收缩。这些模式与个体无关，正如针对单个受试者中不同表位的不一致克隆型特异性转变所证明的那样。此外，长期无症状 HIV-1 感染的特点是 TCR 库的进化与病毒复制并行。总的来说，这些数据表明在TCR-抗原界面上精心策划的HIV-1和病毒特异性CD8+T细胞克隆型之间存在连续的双向适应过程。重要性我们描述了慢性HIV-1感染中病毒表位突变、抗原特异性T细胞扩增和反应克隆型库之间的关系。这项工作提供了对人类免疫系统和快速进化的慢病毒之间的共同适应过程的见解。
Although CD8(+) T cells are important for the control of HIV-1 in vivo, the precise correlates of immune efficacy remain unclear. In this study, we conducted a comprehensive analysis of viral sequence variation and T-cell receptor (TCR) repertoire composition across multiple epitope specificities in a group of antiretroviral treatment-naive individuals chronically infected with HIV-1. A negative correlation was detected between changes in antigen-specific TCR repertoire diversity and CD8(+) T-cell response magnitude, reflecting clonotypic expansions and contractions related to alterations in cognate viral epitope sequences. These patterns were independent of the individual, as evidenced by discordant clonotype-specific transitions directed against different epitopes in single subjects. Moreover, long-term asymptomatic HIV-1 infection was characterized by evolution of the TCR repertoire in parallel with viral replication. Collectively, these data suggest a continuous bidirectional process of adaptation between HIV-1 and virus-specific CD8(+) T-cell clonotypes orchestrated at the TCR-antigen interface.IMPORTANCEWe describe a relation between viral epitope mutation, antigen-specific T-cell expansion, and the repertoire of responding clonotypes in chronic HIV-1 infection. This work provides insights into the process of coadaptation between the human immune system and a rapidly evolving lentivirus.