Abraham Philip Raj, Pathak Niteen, Pradhan Gourango, Sumanlatha Gaddam, Mukhopadhyay Sangita
Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India.
Graduate Studies, Manipal University, Manipal, India.
PLoS One. 2017 Jun 26;12(6):e0179965. doi: 10.1371/journal.pone.0179965. eCollection 2017.
The PPE (proline-proline-glutamic acid) proteins of Mycobacterium tuberculosis are characterized by a conserved N-terminal domain of approximately 180 amino acids and variable C-terminal domain. Since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (TB) as they act as a source of antigenic variation. We have demonstrated earlier that one of the PPE proteins PPE17 (Rv1168c) induces strong B-cell and T-cell responses in active TB disease and also displays a higher antibody titer compared to immunodominant antigens such as ESAT-6, Hsp60 and PPD. However, the immunodominant domain of PPE17 (N-terminal or C-terminal) was not examined in detail. In the present study, we observed that antibody responses elicited in TB patients were directed mostly towards the N-terminal domain of PPE17 (N-PPE17). The antibody generated against N-PPE17 in TB patients did not significantly cross-react with N-terminal domains of other PPE proteins used in this study. Our data suggest that the N-terminal domain of PPE17 protein is immunodominant and could be used as a better serodiagnostic marker than the full-length PPE17 protein.
结核分枝杆菌的脯氨酸-脯氨酸-谷氨酸（PPE）蛋白的特征是具有一个约180个氨基酸的保守N端结构域和可变的C端结构域。自上一个十年以来，这些蛋白在结核病血清诊断中变得非常重要，因为它们是抗原变异的来源。我们之前已经证明，其中一种PPE蛋白PPE17（Rv1168c）在活动性结核病中可诱导强烈的B细胞和T细胞反应，并且与免疫显性抗原如ESAT-6、Hsp60和PPD相比，还显示出更高的抗体滴度。然而，PPE17的免疫显性结构域（N端或C端）并未进行详细研究。在本研究中，我们观察到结核病患者产生的抗体反应主要针对PPE17的N端结构域（N-PPE17）。结核病患者中针对N-PPE17产生的抗体与本研究中使用的其他PPE蛋白的N端结构域没有明显交叉反应。我们的数据表明，PPE17蛋白的N端结构域具有免疫显性，并且与全长PPE17蛋白相比，可作为更好的血清诊断标志物。
