Analysis of the complementarity determining regions β-chain genomic rearrangement using high-throughput sequencing in periphery cytotoxic T lymphocytes of patients with chronic hepatitis B

Abstract

Cytotoxic T lymphocytes (CTLs) are important for the recognition of the hepatitis B virus (HBV), mediating immunoprotective mechanisms and determining the clinical outcome following HBV infection. CTLs recognize the invading virus via the T cell receptor (TCR). The aim of the current study was to investigate the variability of TCR in lymphocytes from patients with chronic hepatitis B and whether TCR genomic recombination is regulated by the current treatment strategies. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with chronic hepatitis B and high-throughput sequencing was performed to analyze the gene expression diversity of β chain complementarity determining region. High-throughput sequencing produced ~380,000 reads. The sequences of V and J family mRNAs of the β chain V area were analyzed and databases were created for all 30 V family and J family genes. Using the Basic Local Alignment Search Tool, 15 genes were identified to be upregulated in the samples following treatment. Among them, the expression of T cell receptor β variable 28 (TRBV28)_T cell receptor β joining 1–5 (TRBJ1.5) and TRBV6_TRBJ2.10 were significantly different in the treated samples compared with samples taken prior to treatment. Genomic recombination patterns of TRBV and TRBJ of the β chain V area were observed to be different in the samples following treatment. The data of the current study demonstrated that the genomic rearrangement of the V and J segments of TCR β chain V area may be associated with the chronic progression of HBV and impact on treatment efficacy.

Mucosal‐associated invariant T‐cells are severely reduced and exhausted in humans with chronic HBV infection

“…By analysing the TCR repertoire of MAIT cells, we showed that peripheral blood MAIT cells in CHBV patients expressed higher levels of TRBV5.1 and TRBV11.2_TRBJ1.5 than intrasinusoidal MAIT cells. Recent reports have shown that TRBV5.1 and TRBV11 are highly associated with CHBV infection 27‐30 . Hence, the high levels of TRBV5.1 and TRBV11.2_TRBJ1.5 may explain why peripheral blood MAIT cells are more activated in response to CHBV infection than intrasinusoidal MAIT cells.…”

Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire

“…TCR IR therefore serves as a "footprint" of immune status (Calis and Rosenberg, 2014). Emerging studies suggest that TCR IR participates in various liver diseases (including viral hepatitis, liver regeneration, hepatocellular carcinoma, primary sclerosing cholangitis, and alcoholic liver disease) (Chen et al, 2016;Huang et al, 2016;Liaskou et al, 2016;Jiang et al, 2018). In this study, we demonstrate the resetting of intrahepatic TCR IR in response to chronic liver injury, showing an intact characteristic of V, D, J, VJ, and VDJ segment usage and the distribution of CDR3 AA clonotypes during liver fibrosis.…”

Intrahepatic T‐Cell Receptor β Immune Repertoire Is Essential for Liver Regeneration

“…The TCR immune repertoire, which has been associated with various liver diseases (including chronic virus hepatitis, hepatocellular carcinoma, and primary biliary cirrhosis), is a potential tool to monitor intrahepatic immune status and the microenvironment. (20,(32)(33)(34) Accumulating studies indicate that PHx induces a series of inflammatory signaling cascades that interact to ensure complete LR. In this process, the immune response itself provides exact identification and has been associated with both hepatic parenchymal and nonparenchymal cell proliferation.…”