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Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection
Authors:Jiezuan Yang  Jiajia Chen  Jianqin He  Yirui Xie  Yixing Zhu  Hongcui Cao  Lanjuan Li
Affiliation:[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou China; [2]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
Abstract:
The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews insubjects with virus infection or cancer. The gene melting spectral pattern (GMSP) canbe used to determine the profile of the TRBV gene family. To explore the portrait ofthe TRBV family in peripheral blood lymphocytes from subjects who have recovered fromacute hepatitis B virus infection (AHI), peripheral blood mononuclear cells (PBMCs)were separated and further sorted into CD4+ and CD8+T-cell subsets. The molecular features of the TRBV complementary determining region 3(CDR3) motifs were determined using GMSP analysis. When a GMSP profile showed asingle peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewedexpansions of multiple TRBV genes were observed among the CD4+ andCD8+ T-cell subsets and the PBMCs. The frequency of monoclonallyexpanded TRBV genes in the CD8+ T-cell subset was significantlyhigher than that of the CD4+ T-cell subset and the PBMCs. Compared toother members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantlyexpressed in the repertoire of peripheral blood lymphocytes in recovered AHIsubjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 werealso detected in the CD4+ and CD8+ T-cell subsets.These results demonstrate the presence of multiple biased TRBV families in recoveredAHI subjects. TRBV11, BV15 and BV20, especially from the CD8+ T-cellsubset, may be relevant to the pathogenesis of subjects with AHI. The preferentiallyselected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potentialtargets for personalized treatments of chronic HBV infection.
Keywords:acute hepatitis B virus infection  gene melting spectral pattern  gene therapy  molecular profile  T-cell receptor beta-chain variable
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