title: Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response.
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.
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Zhai
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Li
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou , China.
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Qi
keywords: Cytotoxic T lymphocytes; Efflux pump; Epitope; Immunotherapy; Mycobacterium tuberculosis