title: Identification of a new tuberculosis antigen recognized by γδ T cell receptor.
abstract: 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.
authors: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors: Xueyan
authors: X
authors: Xi
authors: Xiqin
authors: X
authors: Han
authors: Liang
authors: L
authors: Li
authors: Zhendong
authors: Z
authors: Zhao
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma
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