Abstract
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.
Highlights
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health
The percentages of the top 1, 5, and 10 clones showed no significant differences for either TRD or TRG compared with those in the controls (Figures 2E,F). These results demonstrate that the diversity of the complementary determinant region 3 (CDR3) immune repertoire of γδT cells is significantly reduced in TB patients, indicating that some TB infection-related γδT cells are selectively amplified in TB patients or that certain T-cell receptor (TCR) CDR3 gene fragments are preferentially utilized
ΓδT cells account for only a small percentage (1∼5%) of lymphocytes in human peripheral blood but are abundant in epithelial tissues. γδT cells can initiate a rapid immune response during early infection and have major histocompatibility complex (MHC) non-restriction
Summary
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. According to the Global Tuberculosis Report 2018, worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent. An estimated 10.0 million people fell ill with TB in 2017, and 90% of these people were adults [1]. TB is a chronic infectious disease with persistent pathogens. Conventional antituberculosis drugs sometimes fail to yield good results due to the high rate of drug resistance and the proliferation of multiple drugresistant TB strains. ∼558,000 new patients in 2017 were resistant to rifampicin, while 82% had multidrug-resistant tuberculosis (MDR-TB) [1]. TB is still a worldwide public health problem that must be solved
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