Prospects of Cytomegalovirus-Specific T-Cell Receptors in Clinical Diagnosis and Therapy

Abstract

Human cytomegalovirus (HCMV) is responsible for widespread infections worldwide. In immunocompetent individuals it is typically latent, while infection or reactivation in immunocompromised individuals can result in severe clinical symptoms or even death. Although there has been significant progress in the treatment and diagnosis of HCMV infection in recent years, numerous shortcomings and developmental limitations persist. There is an urgent need to develop innovative, safe, and effective treatments, as well as to explore early and timely diagnostic strategies for HCMV infection. Cell-mediated immune responses are the primary factor controlling HCMV infection and replication, but the protective role of humoral immune responses remains controversial. T-cells, key effector cells of the cellular immune system, are critical for clearing and preventing HCMV infection. The T-cell receptor (TCR) lies at the heart of T-cell immune responses, and its diversity enables the immune system to differentiate between self and non-self. Given the significant influence of cellular immunity on human health and the indispensable role of the TCR in T-cell immune responses, we posit that the impact of TCR on the development of novel diagnostic and prognostic methods, as well as on patient monitoring and management of clinical HCMV infection, will be far-reaching and profound. High-throughput and single-cell sequencing technologies have facilitated unprecedented quantitative detection of TCR diversity. With these current sequencing technologies, researchers have already obtained a vast number of TCR sequences. It is plausible that in the near future studies on TCR repertoires will be instrumental in assessing vaccine efficacy, immunotherapeutic strategies, and the early diagnosis of HCMV infection.