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

PLoS One. 2017 Jun 26;12(6):e0179965. doi: 10.1371/journal.pone.0179965. eCollection 2017.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / biosynthesis*
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Case-Control Studies
  • Cross Reactions
  • Female
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Protein Domains
  • Serologic Tests
  • Tuberculosis / diagnosis
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Immunodominant Epitopes
  • Peptide Fragments
  • Rv1168c protein, Mycobacterium tuberculosis

Grants and funding

PRA was supported by the Research Associateship from the Indian Council of Medical Research, Government of India (80/796/2013-ECD). This work was supported by the Grants from Department of Biotechnology, Government of India (BT/PR11605/NNT/28/758/2014 and BT/PR12817/COE/34/23/2015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.