title: Identification of a novel immunodominant antigen Rv2645 from RD13 with potential as a cell-mediated immunity-based TB diagnostic agent.
abstract: Search for novel specific antigens are urgently needed for the detection of tuberculosis (TB). In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (M.tb)-specific candidate antigen (Rv2645) from DNA segment region of differentiation (RD) 13 of M.tb and investigated T-cell recognition during natural infection in humans and experimental mice. Rv2645-specific IFN-γ levels were much higher in the peripheral blood mononuclear cells (PBMCs) of TB patients than that in healthy donors (HDs) (including Bacille Calmette-Guerin (BCG)-vaccinated donors). The enzyme-linked immunospot (ELISPOT) assay with Rv2645 had a high overall agreement (98.0%) with the results from the clinical T-SPOT.TB with 10-kD culture filtrate protein (CFP10) and 6-kD early secreted antigenic target (ESAT6) peptides. The combination of Rv2645 and CFP10-ESAT6 was better than the individual protein, with increased sensitivity and a similar specificity of 96.0% and 98.2%, respectively. Rv2654 also induced M.tb-specific skin-test responses in heat-inactivated M.tb H37Rv immunized mice. Epitope mapping revealed that Rv264530-44 and Rv2645136-143 may be the dominant T-cell and B-cell epitopes, respectively, of Rv2645. This is the first report demonstrating the Rv2654 is a strongly recognized T-cell antigen that is highly specific for TB and has potential as a novel cell-mediated immunity-based TB diagnostic agent.
authors: State Key Laboratory of Virology, Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Basic Medical Sciences, Donghu Road 165#, Wuhan 430071, Hubei Province, China.
authors: Wei
authors: W
authors: Luo
authors: State Key Laboratory of Virology, Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Basic Medical Sciences, Donghu Road 165#, Wuhan 430071, Hubei Province, China.
authors: Zi-Lu
authors: ZL
authors: Qu
authors: State Key Laboratory of Virology, Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Basic Medical Sciences, Donghu Road 165#, Wuhan 430071, Hubei Province, China.
authors: Yan
authors: Y
authors: Xie
authors: Department of Laboratory Medicine, Wuhan Medical Treatment Center, Wuhan, China.
authors: Jie
authors: J
authors: Xiang
authors: State Key Laboratory of Virology, Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Basic Medical Sciences, Donghu Road 165#, Wuhan 430071, Hubei Province, China. Electronic address: zhangxiaolian@whu.edu.cn.
authors: Xiao-Lian
authors: XL
authors: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology; D007111:Immunity, Cellular; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007371:Interferon-gamma
keywords: Diagnosis; Interferon-gamma release assay (IRGA); M. tuberculosis (M.tb); Region of differentiation (RD); Rv2645; Tuberculosis (TB)