[Deep sequencing of the T cell receptor Vb CDR3 repertoire of peripheral CD4+T cells in primary biliary cirrhosis].

Autor: Bao J; Clinical Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou 510180, China., Xu Q, Zou Y, Gao F, Li F, Li Y, Gao K, Peng X, Pang S, Chen Y, Liu H
Jazyk: čínština
Zdroj: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology [Zhonghua Gan Zang Bing Za Zhi] 2015 Aug; Vol. 23 (8), pp. 580-5.
DOI: 10.3760/cma.j.issn.1007-3418.2015.08.005
Abstrakt: Objective: To determine the immune repertoires of peripheral CD4+T cell receptor (TCR) Vb CDR3 in primary biliary cirrhosis (PBC) and analyze TCR diversity and preferred usage at sequence-level resolution.
Methods: ARM-PCR and high-throughput sequencing were used to obtain millions of TCR Vb CDR3 sequences from peripheral CD4+T cells isolated from 7 patients with PBC and healthy volunteers. All sequencing data were analyzed, together with corresponding clinical information, by bioinformatic software. The Mann-Whitney U test was used for statistical analysis.
Results: The PBC patients showed a lower level of diversity among the peripheral CD4+TCR Vb CDR3 than the healthy volunteers, and patients with higher level progression of the disease showed a greater lack of diversity. In addition, 4 specific preferred-usage amino acid sequences were discovered for the PBC patients: ASSFTGGPVEQY, ASSLISSGNNEQF, ATSRDTLAGGPGDTQY, and SASLEGNTEAF; these sequences were also found in higher frequencies in patients with later stages of PBC.
Conclusions: Decreased TCR Vb CDR3 diversities and specific preferred usage of TCR CDR3 sequences in peripheral CD4+T lymphocytes in PBC suggest that clonal expansion of a large number of CD4+T cells may be an important factor for PBC progression. These data provide a better understanding about the general characteristics of CD4+T cells in PBC patients and related to pathogenesis of the disease, and may provide useful insights into potential targets for immunotherapy.
Databáze: MEDLINE