Comprehensive assessment of peripheral blood TCRβ repertoire in infectious mononucleosis and chronic active EBV infection patients
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.
KeywordsEpstein-Barr virus (EBV) Infectious mononucleosis (IM) Chronic active EBV infection (CAEBV) T cell receptor (TCRβ) repertoire complementarity-determining region 3 (CDR3)
Chronic active EBV infection
T cell receptor β
Hypervariable complementarity-determining region 3
- EBV+ LPD
EBV-associated lymphoproliferative disorders
Cytotoxic T lymphocytes
This study was supported by the National Natural Science Foundation of China (grant no. 81371737) and the Basic Research Program of Shenzhen Innovation Council of China (grant no. JCYJ20130402114702128).
Compliance with ethical standards
All procedures were performed according to the ethical standards of the Declaration of Helsinki involving human subjects in medical research. All participants gave written informed consent.
Conflict of interest
The authors declare that they have no conflict of interest.
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