Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
J Virol. 2015 Jan;89(1):110-9. doi: 10.1128/JVI.01765-14. Epub 2014 Oct 15.
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.
We 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.
尽管 CD8(+)T 细胞对于体内 HIV-1 的控制很重要，但免疫效果的确切相关因素仍不清楚。在这项研究中，我们对一组未经抗逆转录病毒治疗的慢性 HIV-1 感染者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。我们检测到抗原特异性 TCR 库多样性的变化与 CD8(+)T 细胞反应幅度呈负相关，这反映了与同源病毒表位序列变化相关的克隆型扩增和收缩。这些模式与个体无关，因为在单个个体中针对不同表位的不同克隆型特异性转变证明了这一点。此外，长期无症状的 HIV-1 感染的特点是 TCR 库与病毒复制平行进化。总的来说，这些数据表明，HIV-1 和病毒特异性 CD8(+)T 细胞克隆型之间在 TCR-抗原界面上存在持续的双向适应过程。
我们描述了慢性 HIV-1 感染中病毒表位突变、抗原特异性 T 细胞扩增和反应性克隆型库之间的关系。这项工作深入了解了人类免疫系统和快速进化的慢病毒之间的共同适应过程。
