Characterization of the diversity of T cell receptor γδ complementary determinant region 3 in human peripheral blood by Immune Repertoire Sequencing.

γδ T cells function as sentinels in early host response to infections and malignancies. Although γδ T cells are regarded as innate immune cells and recognize antigens in a non-MHC restricted manner, they possess a huge diversity of complementary determinant region 3 (CDR3) of T cell receptor (TCR) generated by the rearrangement of germ-line gene V- (D) -J-C fragments. However, the detailed characteristics of the TCRγδ CDR3 repertoire remain unclear. A comprehensive analysis would answer fundamental questions about the diversity of the TCRγδ CDR3 repertoire and elucidate the mechanism underlying γδ T cell recognition of pathogens and tumor antigens. In this study, we used Immune Repertoire Sequencing (IR-SEQ) to analyze the diversity of TCRγδ CDR3 repertoires from 30 healthy donors. The results show that IR-SEQ had sufficient repeatability to analyze the TCRγδ CDR3 repertoire. The diversity of TCRγδ CDR3 repertoire is quite dispersed and individually different. The TCR δ chain (TRD) repertoire displayed more diversity and less sharing among individuals compared with TCR γ chain (TRG). To our knowledge, this is the first study to use IR-SEQ to characterize the repertoire of TCRγδ CDR3 in human peripheral blood γδ T cells by using IR-SEQ. Our findings provide a basic understanding of the diversity of TCRγδ repertoire in the physiological condition, which provides a clue to the underlying mechanism of γδ T cell recognition of pathogens and tumor antigens.

Chen H ，Zou M ，Teng D ，Zhang J ，He W ... -  《-》

Next-Generation Sequencing Analysis of the Human TCRγδ+ T-Cell Repertoire Reveals Shifts in Vγ- and Vδ-Usage in Memory Populations upon Aging.

Kallemeijn MJ ，Kavelaars FG ，van der Klift MY ，Wolvers-Tettero ILM ，Valk PJM ，van Dongen JJM ，Langerak AW ... -  《Frontiers in Immunology》

Profiling the pattern of the human T-cell receptor γδ complementary determinant region 3 repertoire in patients with lung carcinoma via high-throughput sequencing analysis.

Chen H ，Zou M ，Teng D ，Hu Y ，Zhang J ，He W ... -  《-》

Reconstitution of gammadelta T cell repertoire diversity after human allogeneic hematopoietic cell transplantation and the role of peripheral expansion of mature T cell population in the graft.

Hirokawa M ，Horiuchi T ，Kawabata Y ，Kitabayashi A ，Miura AB ... -  《BONE MARROW TRANSPLANTATION》

Identification of the Ligands of TCRγδ by Screening the Immune Repertoire of γδT Cells From Patients With Tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. γδT cells, which are characterized by major histocompatibility complex (MHC) non-restriction, are rapidly activated and initiate anti-infectious immune responses in the early stages of Mtb infection. However, the mechanism underlying the recognition of Mtb by γδT cells remains unclear. In this study, we characterized the pattern of the human T-cell receptor (TCR) γδ complementary determinant region 3 (CDR3) repertoire in TB patients by using high-throughput immune repertoire sequencing. The results showed that the diversity of CDR3δ was significantly reduced and that the frequency of different gene fragments (V/J), particularly the V-segment of the δ-chain, was substantially altered, which indicate that TB infection-related γδT cells, especially the δ genes, were activated and amplified in TB patients. Then, we screened the Mtb-associated epitopes/proteins recognized by γδT cells using an Mtb proteome chip with dominant CDR3δ peptides as probes. We identified the Mtb protein Rv0002 as a potential ligand capable of stimulating the activation and proliferation of γδT cells. Our findings provide a further understanding of the mechanisms underlying γδT cell-mediated immunity against Mtb infection.

Li Y ，Wang X ，Teng D ，Chen H ，Wang M ，Wang J ，Zhang J ，He W ... -  《Frontiers in Immunology》