Characteristics of the V2 CDR3 Sequence of Peripheral T Cells in Patients with Pulmonary Tuberculosis and Identification of a New Tuberculosis-Related Antigen Peptide

Antigen-specific T cells may play an important role in the immune response toMycobacterium tuberculosis. However, little is known about the characteristics of the length distribution of the 2-chain complementarity determining region 3 (2 CDR3) of the T-cell receptor (TCR) in patients with active pulmonary tuberculosis (TB) on a large scale. In addition,M. tuberculosis-activated T cells potentially inhibit intracellular mycobacterial growth, but phosphoantigen-activated T cells do not. Only a fewM. tuberculosis-related antigen peptides or proteins that are recognized by TCR have been identified. Twenty-four healthy donors (HDs) and 27 TB patients were included in the present study. The gene-scanning technique found that the 2 CDR3 length distribution patterns of TCR in TB patients were perturbed, and each pattern included different predominant CDR3 sequences. The predominant 2 CDR3 sequences of TCRs, which originated from TB patients and HD T cells that were stimulated byM. tuberculosis heat resistance antigen (Mtb-HAg), were used as probes to screen peptides recognized by TCR using a phage display library. We identified four peptides that bound to the predominant 2 CDR3 fragments and showed homology toM. tuberculosis genes in a BLAST search. Notably, one peptide was related toM. tuberculosisH37Rv (QHIPKPP), and this fragment was confirmed as a ligand for the TCR. Two fragments, Ag1 and Ag2, activated T cells fromHD or TB patients. In summary, the 2 CDR3 lineage of TB patients apparently drifts, and the predominant 2 CDR3 sequence that recog-nizesM. tuberculosismay exhibit specificity. The identifiedM. tuberculosis-related antigen peptides may be used as vaccines or adjuvants for protective immunity againstM. tuberculosis