Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains.

Peipei Liu,Juncai Ma,Di Liu,Jing Gao,George F Gao,Jun Wu,Xuyu Zhou,Baoli Zhu,Jing Zou,Fangqing Zhao,Fei Liu,Xi Yang,Yan Chen,Xue Xiao

doi:10.1007/s13238-014-0060-1

Abstract

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 analyzed the diversity and complexity of both the TCRα 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-014-0060-1) contains supplementary material, which is available to authorized users.

Highlights

The T lymphocytes that are engaged in cellular immunity are mainly αβ T cells
We found that the diversity of the T-cell receptor (TCR) α chain (TRA) repertoire is higher than that of the TCR β chain (TRB) repertoire, and the usage of V and J gene segments was preferential for both chains, though the overall frequency pattern was conserved among different individuals
The 5′ rapid amplification of cDNA ends (5′RACE) approach avoids the potential bias associated with the use of the multiple primer sets required to amplify all V region sequences and takes advantage of the conserved sequences offered by TRAC for TRA and TRBC1 and TRBC2 (96% nucleotide sequence identity) for TRB1

Summary

Introduction

The T lymphocytes that are engaged in cellular immunity are mainly αβ T cells. The T-cell receptors (TCRs) located on the Electronic supplementary material The online version of this article (doi:10.1007/s13238-014-0060-1) contains supplementary material, which is available to authorized users.T cell surface play key roles in recognition of the vast number of antigenic peptides presented by the major histocompatibility complex (p-MHC). The T lymphocytes that are engaged in cellular immunity are mainly αβ T cells. The T-cell receptors (TCRs) located on the Electronic supplementary material The online version of this article (doi:10.1007/s13238-014-0060-1) contains supplementary material, which is available to authorized users. Heterodimeric TCRs are composed of two polypeptide chains, the α and the β chains, each containing one variable domain and one constant domain (Murphy et al, 2007). The antigenic specificity of T lymphocytes is primarily determined by the amino acid sequences of the hypervariable complementarity determining region 3 (CDR3). The nucleotide sequences of CDR3 are generated by somatic recombination of segregated germline variable (V), diversity (D), and joining (J) gene segments for the TCR β chain (TRB), and V and J gene segments for the TCR α chain (TRA)

Methods

Results

Conclusion