Division of Immunology and Allergy, Department of Medicine, University Hospital Center, University of Lausanne, 1011 Lausanne, Switzerland.
J Immunol. 2011 Jun 15;186(12):7039-49. doi: 10.4049/jimmunol.1003309. Epub 2011 May 9.
Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR β-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤ 80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤ 9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.
通过锚定 PCR 对病毒特异性 CD8 T 细胞群体进行的离体分析表明，CD8 TCR 库的寡克隆性（每个个体表位 7 到 9 个克隆型）低于先前的预期。在目前的研究中，通过评估来自 27 名健康供体的离体分离的 CMV 和 EBV 特异性 CD8 T 细胞中的总体 TCR β 链可变区使用情况以及 CDR3 区，研究了 TCR 多样性。大多数单个病毒表位特异性的克隆型数量在 14 到 77 之间。在 HIV-1 慢性感染（即病毒复制受抑制以及治疗中断和 Ag 再暴露后）的条件下，还进行了 CD8 TCR 库的纵向评估。结果表明，Ag 再暴露后发生了大量的 TRB 库更新（≤80%），最终与 T 细胞识别功能亲和力的增加相关。这些结果表明，整体 CD8 TCR 库的多样性（≤9 倍）远高于先前的估计，并为支持慢性病毒感染和 Ag 再暴露期间的大规模库更新提供了机制基础。
