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鉴定结核分枝杆菌外排泵的新型 T 细胞表位。

Identification of novel T cell epitopes from efflux pumps of Mycobacterium tuberculosis.

机构信息

Department of Bioengineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.

出版信息

Immunol Lett. 2011 Oct 30;140(1-2):68-73. doi: 10.1016/j.imlet.2011.06.009. Epub 2011 Jul 3.

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-A0201 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-A02(+), 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.

摘要

细胞毒性 T 淋巴细胞(CTL)在结核分枝杆菌(Mtb)感染的免疫中发挥重要作用。本研究报道了从外排泵 Rv1258c 和 Rv1410c 中鉴定新的 CTL 表位。使用预测程序预测候选天然肽及其类似物。Rv1410c-p510(TLAPQVEPL)和 Rv1410c-p510-1Y9V(YLAPQVEPV)与 HLA-A0201 分子具有很强的结合亲和力和稳定性。在酶联免疫斑点(ELISPOT)测定中,这些肽诱导的外周血单个核细胞(PBMC)中的 CTL 至少在一个健康供体(HLA-A02(+),PPD(+))中释放干扰素-γ(IFN-γ)。在体外和体内细胞毒性测定中,Rv1410c-p510-1Y9V 诱导的 CTL 可特异性裂解载肽的 T2 细胞。这是首次从 Mtb 的外排泵中鉴定 CTL 表位的报道。鉴定的新表位可作为针对耐药结核分枝杆菌的多价肽疫苗的候选物。

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