Identification of a new tuberculosis antigen recognized by gammadelta T cell receptor. Clin Vaccine Immunol 20:530–539

The immune protection initiated by T cells plays an important role in mycobacterial infection. The T cells activated by Mycobacterium tuberculosis-derived nonpeptidic, phosphorylated biometabolites (phosphoantigens) provide only partial im-mune protection against mycobacterium, while evidence has suggested that protein antigen-activated 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 T cells using cells transfected with the predominant pulmonary tuberculo-sis T cell receptor (TCR) CDR3 fragment. We identified two peptides, TP1 and TP2, which not only bind to the pulmonary tuberculosis predominant TCR but also effectively activate T cells isolated from pulmonary tuberculosis patients. More-over, 1-deoxy-D-xylulose 5-phosphate synthase 2 (DXS2), the TP1-matchedmycobacterial protein, was confirmed as a ligand for the TCR and was found to activate T cells from pulmonary tuberculosis patients. The extracellular region (extracellular peptide [EP]) of Rv2272, a TP2-matchedmycobacterial transmembrane protein, was also shown to activate T cells from pul-monary tuberculosis patients. Both DXS2- and EP-expanded T cells from pulmonary tuberculosis patients could secrete gamma interferon (IFN-) andmonocyte chemoattractant protein 1 (MCP-1), which play important roles in mediating cytotox-icity against mycobacterium and stimulating monocyte chemotaxis toward the site of infection. In conclusion, our study identi-fied novel mycobacterial protein antigens recognized by TCR cells that could be candidates for the development of vaccines or adjuvants against mycobacterium infection