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Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response

, , , , , ,
  School of Life Sciences, Zhengzhou University, Zhengzhou, China
DOI
10.7287/peerj.preprints.987v1
Published
Accepted
Subject Areas
Biochemistry, Microbiology, Immunology
Keywords
cytotoxic T lymphocytes, efflux pump, epitope, immunotherapy, Mycobacterium tuberculosis
Copyright
© 2015 Zhai et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
Cite this article
Zhai M, Chen F, Zhao Y, Wu Y, Li G, Gao Y, Qi Y. 2015. Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response. PeerJ PrePrints 3:e987v1

Abstract

Overcoming drug-resistance is one of the major challenges to control tuberculosis (TB). The up-regulation of efflux pumps is one common mechanism that leads to drug-resistance. Therefore, immunotherapy targeting these efflux pump antigens could be promising strategy to be combined with current chemotherapy. Considering that CD8+ cytotoxic T lymphocytes (CTLs) induced by antigenic peptides (epitopes) could elicit HLA-restricted anti-TB immune response, efflux pumps from classical ABC family (Mycobacterium tuberculosis, Mtb) were chosen as target antigens to identify CTL epitopes. HLA-A2 restricted candidate peptides from Rv2937, Rv2686c and Rv2687c of Mycobacterium tuberculosis were predicted, synthesized and tested. Five peptides could induce IFN-γ release and cytotoxic activity in PBMCs from HLA-A2+ PPD+ donors. Results from HLA-A2/Kb transgenic mice immunization assay suggested that four peptides Rv2937-p168, Rv2937-p266, Rv2686c-p151, and Rv2686c-p181 could induce significant CTL response in vivo. These results suggested that these novel epitopes could be used as immunotherapy candidates to TB drug-resistance.

Author Comment

This is a submission to PeerJ for review.

Supplemental Information

Data of CTL lysis activity from PPD- donor

DOI: 10.7287/peerj.preprints.987v1/supp-1

Additional Information

Competing Interests

The authors declare they have no competing interests.

Author Contributions

Mingxia Zhai performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Fei Chen performed the experiments, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Yuanyuan Zhao performed the experiments, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Yahong Wu performed the experiments, reviewed drafts of the paper.

Guodong Li analyzed the data, contributed reagents/materials/analysis tools, reviewed drafts of the paper.

Yanfeng Gao conceived and designed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Yuanming Qi conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.

Human Ethics

The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):

This project was reviewed and approved by the Ethics Committee of Zhengzhou University. The sample collection from healthy donors and animal experiment were performed according to the guidance of the Ethics Committee of Zhengzhou University (#20120312)

Animal Ethics

The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):

This project was reviewed and approved by the Ethics Committee of Zhengzhou University. The sample collection from healthy donors and animal experiment were performed according to the guidance of the Ethics Committee of Zhengzhou University (#20120312)

Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81273228, 81373228) and grants from the Outstanding Talent Project of Henan Province (134100510015) and Zhengzhou University (1421311081). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response
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