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

Ming-Xia Zhai; Fei Chen; Yuan-Yuan Zhao; Ya-Hong Wu; Guo-Dong Li; Yan-Feng Gao; Yuan-Ming Qi

doi:10.7717/peerj.1229

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

PeerJ. 2015 Sep 22:3:e1229. doi: 10.7717/peerj.1229. eCollection 2015.

Authors

Ming-Xia Zhai¹, Fei Chen¹, Yuan-Yuan Zhao¹, Ya-Hong Wu¹, Guo-Dong Li¹, Yan-Feng Gao¹, Yuan-Ming Qi¹

Affiliation

¹ School of Life Sciences, Zhengzhou University , Zhengzhou , China.

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/K(b) 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.

Keywords: Cytotoxic T lymphocytes; Efflux pump; Epitope; Immunotherapy; Mycobacterium tuberculosis.

Grants and 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.