Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response.
Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response.
复制标题
从结核分枝杆菌外排泵中鉴定出的新表位可诱导细胞毒性 T 淋巴细胞反应
作者：
Zhai MX;Chen F;Zhao YY;Wu YH;Li GD;Gao YF;Qi YM
克服耐药性是控制结核病的主要挑战之一。外排泵的上调是导致耐药的一种常见机制。因此，针对这些外排泵抗原的免疫治疗可能是与当前化疗联合的有希望的策略。考虑到抗原肽（表位）诱导的CD8+细胞毒性T淋巴细胞（CTL）可引起hla限制性抗结核免疫应答，我们选择经典ABC家族（Mycobacterium tuberculosis, Mtb）的外排泵作为靶抗原来鉴定CTL表位。对结核分枝杆菌Rv2937、Rv2686c和Rv2687c的HLA-A2限制性候选肽进行了预测、合成和检测。5种多肽可诱导HLA-A2+ PPD+供者外周血中IFN-γ的释放和细胞毒活性。HLA-A2/Kb转基因小鼠免疫实验结果表明，Rv2937-p168、Rv2937-p266、Rv2686c-p151和Rv2686c-p181四种多肽在体内可诱导显著的CTL应答。这些结果表明，这些新的表位可以作为结核病耐药的免疫治疗候选。
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.