The characterization of the human T-cell receptor （TCR） repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we ana- lyzed the diversity and complexity of both the TCRa ...The characterization of the human T-cell receptor （TCR） repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we ana- lyzed the diversity and complexity of both the TCRa and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene （TRAV42/DV1）. Moreover, we uncovered the presence of tandem TRBD （TRB D gene） usage in -2% of the productive human TCRβ CDR3 sequences.展开更多
乙型肝炎病毒(hepatitis B virus,HBV)感染一直以来都是世界范围内严重的公共卫生问题,可导致急、慢性肝脏疾病以及多种并发症。接种HBV疫苗诱导机体B细胞分泌保护性的乙型肝炎病毒表面抗体(hepatitis B surface antibody,HBsAb)是预防...乙型肝炎病毒(hepatitis B virus,HBV)感染一直以来都是世界范围内严重的公共卫生问题,可导致急、慢性肝脏疾病以及多种并发症。接种HBV疫苗诱导机体B细胞分泌保护性的乙型肝炎病毒表面抗体(hepatitis B surface antibody,HBsAb)是预防HBV感染最重要的措施。研究表明不同个体对HBV疫苗应答的效应不一致,可分为超高/高、正常/中等、低/无应答,对其产生机制的研究可为高滴度HBsAb制备、HBV感染防治等提供参考。本文将对HBV疫苗接种后不同应答效应个体B细胞特征和机制的研究概况与进展进行综述。展开更多
γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the ...γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the antitumor immune response.In this study,we characterized the pattern of the human TCRγδcomplementary determinant region 3(CDR3)repertoire in patients with lung carcinoma(LC)via high-throughput sequencing.The results showed that the diversity of CDR3δwas significantly reduced,and that of CDR3γwas unchanged in LC patients compared with healthy individuals;in addition,LC patients shared significantly more CDR3δsequences with each other than healthy individuals.The CDR3 length distribution and N-addition length distribution did not significantly differ between LC patients and healthy individuals.In addition,the CDR3 repertoire tended to use more Vδ2 and fewer Vδ1 germline gene fragments among LC patients.Moreover,we found a combination of four TCRγδrepertoire features that focus on CDR3δand can be used as a biomarker for LC diagnosis.Our research suggests that the TCRγδCDR3 repertoire changed in LC patients due to the antitumor immune response byγδT cells in vivo,and these changes primarily focus on the amplification of certain tumor-specific CDR3δclones among patients.This study demonstrates the role ofγδT cells from the TCRγδCDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function ofγδT cells in antitumor immunity.展开更多
基金We thank Dr. Christopher J. Vavrickafor and Boris Tefsen for their critical reading and revision of the manuscript and Dr. Miles P. Dav- enport for his inspiring discussions. This work is supported by the National Natural Science Foundation of China （NSFC, Grant No. 31030030）, the National Basic Research Program （973 Program） （No. 2013CB531500） and the National Natural Science Foundation of China （Grant No. 81373141 ）. G.F.G. is a leading principal investigator of the NSFC Innovative Research Group （Grant No. 81321063）.
文摘The characterization of the human T-cell receptor （TCR） repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we ana- lyzed the diversity and complexity of both the TCRa and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene （TRAV42/DV1）. Moreover, we uncovered the presence of tandem TRBD （TRB D gene） usage in -2% of the productive human TCRβ CDR3 sequences.
文摘乙型肝炎病毒(hepatitis B virus,HBV)感染一直以来都是世界范围内严重的公共卫生问题,可导致急、慢性肝脏疾病以及多种并发症。接种HBV疫苗诱导机体B细胞分泌保护性的乙型肝炎病毒表面抗体(hepatitis B surface antibody,HBsAb)是预防HBV感染最重要的措施。研究表明不同个体对HBV疫苗应答的效应不一致,可分为超高/高、正常/中等、低/无应答,对其产生机制的研究可为高滴度HBsAb制备、HBV感染防治等提供参考。本文将对HBV疫苗接种后不同应答效应个体B细胞特征和机制的研究概况与进展进行综述。
基金by the National Natural Science Foundation of China(31500725,81673010,91542117,81471574,31471016)CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses(2016ZX310180-5 and 2017PT31004)+2 种基金the CAMS Initiative for Innovative Medicine(2016-I2M-1-008)the National Key Research and Development Program of China(2016YFA0101001,2016YFC0903900)Peking Union Medical College Foundation(No.3332015111).
文摘γδT cells function as sentinels in early host responses to infections and malignancies.Specifically,γδT cells recognize tumor-associated stress antigens via T-cell receptor(TCR)γδand play important roles in the antitumor immune response.In this study,we characterized the pattern of the human TCRγδcomplementary determinant region 3(CDR3)repertoire in patients with lung carcinoma(LC)via high-throughput sequencing.The results showed that the diversity of CDR3δwas significantly reduced,and that of CDR3γwas unchanged in LC patients compared with healthy individuals;in addition,LC patients shared significantly more CDR3δsequences with each other than healthy individuals.The CDR3 length distribution and N-addition length distribution did not significantly differ between LC patients and healthy individuals.In addition,the CDR3 repertoire tended to use more Vδ2 and fewer Vδ1 germline gene fragments among LC patients.Moreover,we found a combination of four TCRγδrepertoire features that focus on CDR3δand can be used as a biomarker for LC diagnosis.Our research suggests that the TCRγδCDR3 repertoire changed in LC patients due to the antitumor immune response byγδT cells in vivo,and these changes primarily focus on the amplification of certain tumor-specific CDR3δclones among patients.This study demonstrates the role ofγδT cells from the TCRγδCDR3 repertoire in tumor immunity and lays the foundation for elucidating the mechanism underlying the function ofγδT cells in antitumor immunity.
