An analysis of T cell antigen receptor variable β genes during the clinical course of patients with chronic hepatitis B

Sugyo, Shinya; Yuh, Kouichi; Nakamura, Ken; Emi, Kanako; Shijo, Hiroshi; Iida, Takeshi; Kimura, N.; Tamura, Kazuo

doi:10.1046/j.1440-1746.1999.01854.x

Cited by 4 publications

(3 citation statements)

References 33 publications

(41 reference statements)

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“…This is in contrast with previous studies, where TCR CDR3 size diversity was analyzed in a combined population of CD4+ and CD8+ T cells obtained from patients with CHB (18, 19). …”

Section: Discussioncontrasting

confidence: 58%

Analysis of T Cell Receptor Vβ Diversity in Peripheral CD4+ and CD8+ T Lymphocytes Obtained From Patients With Chronic Severe Hepatitis B

2014

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Background:The hepatitis B virus (HBV) antigen-induced cellular immune response plays an important role in HBV clearance. Changes in the diversity of complementarity determining region 3 (CDR3) and T-cell receptor (TCR) sequences are used to monitor the response of T cells to antigens.Objectives:The aim of the present study was to determine whether the TCR Vβ repertoire of patients with chronic severe hepatitis B (CSHB) undergoes increased stimulation, and to identify conserved motifs in specific TCR Vβ families.Patients and Methods:Peripheral blood mononuclear cells (PBMCs) from 18 patients with CSHB were sorted into CD4+ and CD8+ T subsets, using monoclonal antibody-coated magnetic beads. The TCR Vβ CDR3 was subsequently characterized using immune spectratyping. The TCR Vβ families exhibiting a CDR3 spectratype that underwent monoclonal expansion were sequenced.Results:The number of oligoclonal or monoclonal expansion TCR Vβ families detected in the analyzed CD8+ T cells was significantly higher than the number detected in CD4+ T cells. The CDR3 spectratype analysis showed predominant usage of TCR Vβ5, Vβ7, Vβ9, Vβ12, and Vβ18 families in CD8+ T cell subsets of CSHB patients. Furthermore, conserved amino acid motifs were found to be associated with the monoclonal expansion of CD8+ TCR Vβ families. In addition, JB1S1 and JB2S7 region genes were present at a high frequency.Conclusions:The CD4+ and CD8+ TCR Vβ gene families undergo clonal expansion in CSHB patients, and CD8+ T cells play a major role in the pathogenesis of CSHB. Moreover, the conserved motifs and limited use of joining region genes observed in the CSHB patients of this cohort indicated that similar antigenic epitopes are recognized.

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“…This is in contrast with previous studies, where TCR CDR3 size diversity was analyzed in a combined population of CD4+ and CD8+ T cells obtained from patients with CHB (18, 19). …”

Section: Discussioncontrasting

confidence: 58%

Analysis of T Cell Receptor Vβ Diversity in Peripheral CD4+ and CD8+ T Lymphocytes Obtained From Patients With Chronic Severe Hepatitis B

2014

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“…Sugyo et al [27] monitored the TCR β chains of 4 healthy controls from 4 to 8 weeks, revealing that there was no significant change in the ratio. Many studies have confirmed that, in patients with viral infection or cancer, the frequency of antigen-specific TCRs differs [28, 29].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

Huang

Liu

et al. 2016

Canadian Journal of Infectious Diseases and Medical Microbiolog

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T lymphocytes are the most important immune cells that affect both the development and treatment of hepatitis B. We used high-throughput sequencing to determine the diversity in the V and J regions of the TCRβ chain in 4 chronic hepatitis B patients before and after HBeAg seroconversion. Here, we demonstrate that the 4 patients expressed Vβ12-4 at the highest frequencies of 10.6%, 9.2%, 17.5%, and 7.5%, and Vβ28 was the second most common, with frequencies of 7.8%, 6.7%, 5.3%, and 10.9%, respectively. No significant changes were observed following seroconversion. With regard to the Jβ gene, Jβ2-1 was the most commonly expressed in the 4 patients at frequencies of 5.8%, 6.5%, 11.3%, and 7.3%, respectively. Analysis of the V-J region genes revealed several differences, including significant increases in the expression levels of V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 and a decrease in that of V19-01-J2-3. These results illustrate the presence of biased TCRVβ and Jβ gene expression in the chronic hepatitis B patients. TRBVβ12-4, Vβ28, Jβ2-1, V7-2-01-J2-1, V12-4-J1-1, and V28-1-J1-5 may be associated with the development and treatment of CHB.

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“…Several techniques have been applied to analyze human TCR usage such as analysis with monoclonal antibodies specific for TCR V regions [17,18] or analysis by the polymerase chain reaction (PCR) with a primer located in C gene and different V gene family-specific primers [19][20][21][22][23][24]. However, these methods do not correctly reflect TCR usage nor do they provide detailed information on J gene segments or CDR3 sequences.…”

Section: Introductionmentioning

confidence: 99%

Analysis of T Cell Receptor Variable Regions and Complementarity Determining Region 3 of Infiltrating T Lymphocytes in the Liver of Patients with Chronic Type B Hepatitis

et al. 2003

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Objectives: T cell receptor (TCR) variable regions and complementarity determining regions 3 (CDR3) of infiltrating T cells in the livers of patients with chronic hepatitis B were examined in detail. Methods: TCR usage was examined by the inverse polymerase chain reaction in 2 hepatitis B e antigen-positive patients, one at an early stage and the other at an advanced stage. Results: In 61 productively rearranged clones bearing TCRα genes in the liver of the patient with early stage chronic hepatitis B, the Vα 7.2 gene segment was most frequently used (16.4%), while the other Vα gene segments were used less frequently. All but one of the clones with the Vα7.2 gene were joined with the Jα33 gene, and the CDR3 regions of these clones were the same length and similar in amino acid sequence. In contrast, in 68 productively rearranged clones from the liver of the patient with advanced stage disease, all Vα gene segments were used less frequently, and combinations of the Vα and Jα gene segments varied. Conclusions: Our data suggest a relatively restricted usage of TCR in the liver in early stage chronic hepatitis B.

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An analysis of T cell antigen receptor variable β genes during the clinical course of patients with chronic hepatitis B

Abstract: These findings suggest that the skewing of the TcR family with multiclone is the result of T-cell responses to viral antigens in peripheral blood.

Cited by 4 publications

References 33 publications

Analysis of T Cell Receptor Vβ Diversity in Peripheral CD4+ and CD8+ T Lymphocytes Obtained From Patients With Chronic Severe Hepatitis B

Analysis of T Cell Receptor Vβ Diversity in Peripheral CD4+ and CD8+ T Lymphocytes Obtained From Patients With Chronic Severe Hepatitis B

High-Throughput Analysis of the T Cell Receptor Beta Chain Repertoire in PBMCs from Chronic Hepatitis B Patients with HBeAg Seroconversion

Analysis of T Cell Receptor Variable Regions and Complementarity Determining Region 3 of Infiltrating T Lymphocytes in the Liver of Patients with Chronic Type B Hepatitis

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