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The N-terminal domain of Mycobacterium tuberculosis PPE17 (Rv1168c) protein plays a dominant role in inducing antibody responses in active TB patients

机译:结核分枝杆菌PPE17(Rv1168c)蛋白的N末端结构域在活跃的结核病患者中诱导抗体反应中起主要作用

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摘要

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.
机译:结核分枝杆菌的PPE(脯氨酸-脯氨酸-谷氨酸)蛋白的特征是大约180个氨基酸的保守N末端结构域和可变的C末端结构域。自上个十年以来,这些蛋白质在结核病(TB)的血清学诊断中已变得非常重要,因为它们是抗原变异的来源。早先我们已经证明,一种PPE蛋白PPE17(Rv1168c)在活动性TB疾病中诱导强烈的B细胞和T细胞反应,并且与诸如ESAT-6,Hsp60和PPD等免疫优势抗原相比,还显示出更高的抗体效价。但是,没有详细检查PPE17的免疫优势结构域(N端或C端)。在本研究中,我们观察到在结核病患者中引起的抗体反应主要针对PPE17(N-PPE17)的N末端结构域。在结核病患者中针对N-PPE17生成的抗体与本研究中使用的其他PPE蛋白的N末端结构域没有明显的交叉反应。我们的数据表明,PPE17蛋白的N末端结构域具有免疫优势,可以用作比全长PPE17蛋白更好的血清诊断指标。

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