Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
Focus Group 'Clinical Cell Processing and Purification', Institute for Advanced Study, TUM, Munich, Germany.
Immunol Rev. 2018 May;283(1):113-128. doi: 10.1111/imr.12654.
During infections and cancer, the composition of the T-cell receptor (TCR) repertoire of antigen-specific CD8 T cells changes over time. TCR avidity is thought to be a major driver of this process, thereby interacting with several additional regulators of T-cell responses to form a composite immune response architecture. Infections with latent viruses, such as cytomegalovirus (CMV), can lead to large T-cell responses characterized by an oligoclonal TCR repertoire. Here, we review the current status of experimental studies and theoretical models of TCR repertoire evolution during CMV infection. We will particularly discuss the degree to which this process may be determined through structural TCR avidity. As engineered TCR-redirected T cells have moved into the spotlight for providing more effective immunotherapies, it is essential to understand how the key features of a given TCR influence T-cell expansion and maintenance in settings of infection or malignancy. Deeper insights into these mechanisms will improve our basic understanding of T-cell immunology and help to identify optimal TCRs for immunotherapy.
在感染和癌症期间，抗原特异性 CD8 T 细胞的 T 细胞受体 (TCR) 谱的组成随时间发生变化。TCR 亲合力被认为是该过程的主要驱动因素，从而与 T 细胞反应的几个其他调节剂相互作用，形成复合免疫反应结构。潜伏病毒（如巨细胞病毒 (CMV)）的感染可导致以寡克隆 TCR 谱为特征的大型 T 细胞反应。在这里，我们回顾了 CMV 感染期间 TCR 谱进化的实验研究和理论模型的现状。我们将特别讨论这一过程在多大程度上可能通过结构 TCR 亲合力来决定。随着工程 TCR 重定向 T 细胞成为提供更有效免疫疗法的焦点，了解给定 TCR 的关键特征如何影响感染或恶性肿瘤环境中的 T 细胞扩增和维持至关重要。对这些机制的更深入了解将提高我们对 T 细胞免疫学的基本理解，并有助于为免疫疗法确定最佳 TCR。
