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.
Department of Laboratory Medicine, Wuhan Medical Treatment Center, Wuhan, China.
J Infect. 2015 Nov;71(5):534-43. doi: 10.1016/j.jinf.2015.07.011. Epub 2015 Aug 28.
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.
寻找新型特异性抗原对于结核病（TB）的检测至关重要。在这项研究中，我们评估了来自结核分枝杆菌（M.tb）DNA 区分区（RD）13 的新型 M.tb 特异性候选抗原（Rv2645）的诊断潜力，并研究了其在人类和实验小鼠自然感染中的 T 细胞识别。TB 患者外周血单核细胞（PBMC）中的 Rv2645 特异性 IFN-γ水平明显高于健康供体（HDs）（包括卡介苗（BCG）接种供体）。Rv2645 的酶联免疫斑点（ELISPOT）检测与临床 T-SPOT.TB 与 10-kD 培养滤液蛋白（CFP10）和 6-kD 早期分泌抗原靶（ESAT6）肽的结果具有很高的总体一致性（98.0%）。Rv2645 与 CFP10-ESAT6 的组合优于单独的蛋白，其敏感性分别提高到 96.0%和 98.2%，特异性相似。Rv2654 还可诱导经热灭活的 M.tb H37Rv 免疫小鼠产生 M.tb 特异性皮肤试验反应。表位映射显示 Rv264530-44 和 Rv2645136-143 可能分别是 Rv2645 的主要 T 细胞和 B 细胞表位。这是首次报道 Rv2654 是一种强烈识别的 T 细胞抗原，对结核病具有高度特异性，并具有作为新型细胞介导免疫为基础的结核病诊断试剂的潜力。
