TCR repertoire evolution during maintenance of CMV-specific T-cell populations

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.