title: Identification of novel T cell epitopes from efflux pumps of Mycobacterium tuberculosis.
abstract: Cytotoxic T lymphocytes (CTLs) play an important role in the immunity of Mycobacterium tuberculosis (Mtb) infection. In the present study, the identification of novel CTL epitopes from efflux pumps, Rv1258c and Rv1410c, was reported. Candidate native peptides and their analogues were predicted with prediction programs. Rv1410c-p510 (TLAPQVEPL) and Rv1410c-p510-1Y9V (YLAPQVEPV) showed potent binding affinity and stability towards HLA-A*0201 molecule. In enzyme-linked immunospot (ELISPOT) assay, the CTLs induced from peripheral blood mononuclear cells (PBMCs) by these peptides could release interferon-γ (IFN-γ) in at least one healthy donor (HLA-A*02(+), PPD(+)). In cytotoxicity assay in vitro and in vivo, the CTLs induced by Rv1410c-p510-1Y9V could specifically lyse peptide-loaded T2 cells. This is the first report to identify CTL epitopes from the efflux pumps of Mtb. The novel epitope identified could serve as candidate to the multivalent peptide vaccine against drug-resistant M. tuberculosis.
authors.affiliation: Department of Bioengineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
authors.forename: Yu-Huang
authors.initials: YH
authors.lastname: Zhu
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Gao
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Zhai
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zhai
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Qi
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003198:Computer Simulation; D003602:Cytotoxicity, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D026901:Membrane Transport Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D026901:Membrane Transport Proteins; C425143:P55 protein, Mycobacterium; D010446:Peptide Fragments; C519050:Rv1258c protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma