Profiling the T-cell receptor repertoire of patient with pleural tuberculosis by high-throughput sequencing

Abstract

Pleural tuberculosis (PLTB), a major cause of morbidity and mortality, is the most common extrapulmonary manifestation of active Mycobacterium tuberculosis (Mtb) in developing countries. Gamma delta T-cell receptor (TCR) repertoire of peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) and beta TCR repertoire from peripheral blood mononuclear cells (PBMCs) have been reported. However, a detailed different characteristic of beta TCR repertoire of mononuclear cells isolated from peripheral blood and pleural fluid in the immune response to Mtb infection should be further revealed. The TCR β-chain (TRB) from PBMCs and PEMCs from an untreated pleural tuberculosis patient was sequenced by the Illumina sequencing platform. A total of 96,758 and 124,130 unique complementarity-determining region 3 (CDR3) sequences were identified at the nucleotide level, encoding 69,488 and 99,095 peptide sequences, respectively. TCR profiling showed that TRBV20-1 family and TRBV20-1/TRBJ1-5 gene combination had a dominant expression in PEMCs, but not in PBMCs. Expansive expression of common CDR3 clonotypes was observed in PEMCs. CDR3 spectratyping analysis showed that few TRBV families had a significantly skewed pattern, with one peak or a few prominent peaks in the PBMCs. By contrast, some TRBV families showed oligoclonal or clonal expansion in the PEMCs. Here, we firstly profiled the TRB repertoire differences of PBMCs and PEMCs from one PLTB patient using high-throughput sequencing. And this study may provide new insight for the detailed and efficient study of TCR repertoire of PEMCs in the future.