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

Abstract

Tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) 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 <i>Mtb</i> infection. However, the mechanism underlying the recognition of <i>Mtb</i> 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 (<i>V</i>/<i>J</i>), particularly the <i>V</i>-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 <i>Mtb</i>-associated epitopes/proteins recognized by γδT cells using an <i>Mtb</i> proteome chip with dominant CDR3δ peptides as probes. We identified the <i>Mtb</i> 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 <i>Mtb</i> infection.