The immune protection initiated by γδ T cells plays an important role in mycobacterial
infection. The γδ T cells activated by Mycobacterium tuberculosis-derived nonpeptidic, phosphorylated biometabolites (phosphoantigens) provide only partial immune protection against mycobacterium, while evidence has suggested that
protein antigen-activated γδ T cells elicit effective protective immune responses. To date, only a few distinct mycobacterial
protein antigens have been identified. In the present study, we screened
protein antigens recognized by γδ T cells using cells transfected with the predominant
pulmonary tuberculosis γδ
T cell receptor (TCR) CDR3 fragment. We identified two
peptides, TP1 and TP2, which not only bind to the
pulmonary tuberculosis predominant γδ TCR but also effectively activate γδ T cells isolated from
pulmonary tuberculosis patients. Moreover,
1-deoxy-d-xylulose 5-phosphate synthase 2 (DXS2), the TP1-matched mycobacterial
protein, was confirmed as a
ligand for the γδ TCR and was found to activate γδ T cells from
pulmonary tuberculosis patients. The extracellular region (extracellular
peptide [EP]) of Rv2272, a TP2-matched mycobacterial transmembrane
protein, was also shown to activate γδ T cells from
pulmonary tuberculosis patients. Both DXS2- and EP-expanded γδ T cells from
pulmonary tuberculosis patients could secrete
gamma interferon (IFN-γ) and
monocyte chemoattractant protein 1 (MCP-1), which play important roles in mediating cytotoxicity against mycobacterium and stimulating monocyte chemotaxis toward the site of
infection. In conclusion, our study identified novel mycobacterial
protein antigens recognized by γδ TCR cells that could be candidates for the development of
vaccines or adjuvants against
mycobacterium infection.