Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis.
Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis.
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DOI：
10.1155/2021/8899674
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发表时间：
2021
影响因子：
4.1
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Lin Y;Dong Y;Gao Y;Shi R;Li Y;Zhou X;Liu W;Li G;Qi Y;Wu Y
结核病是世界上最致命的传染病，每年有 1000 万人患病，150 万人死于该病。随着结核分枝杆菌（MTB）耐药菌株数量的不断增加以及MTB与人类免疫缺陷病毒合并感染的流行，结核病的防治仍面临许多挑战。因此，开发安全有效的结核疫苗是一个紧迫的问题。在这项研究中，我们鉴定了 MTB 耐药相关膜蛋白流出泵、ATP 结合盒和主要促进子超家族上的细胞毒性 T 淋巴细胞表位。首先，使用三个在线软件来预测 HLA-A2 限制性表位。然后，通过T2A2细胞结合亲和力、肽/MHC（pMHC）复合物稳定性测定和体外免疫活性实验来确认候选表位。选择了两种耐药 T 淋巴细胞表位，命名为 Rv1218c-p24 和 Rv2477c-p182，并在基因工程小鼠体内研究了它们的免疫原性活性。在弗氏完全佐剂（CFA）的帮助下，这两个表位的免疫活性得到了提高。这里确定的表位为耐药感染患者的诊断和治疗以及未来多表位疫苗的开发提供了基础。
Tuberculosis is the world's most deadly infectious disease, with 10 million people falling ill and 1.5 million people dying from the disease every year. With the increasing number of drug-resistant Mycobacterium tuberculosis (MTB) strains and prevalence of coinfection of MTB with human immunodeficiency virus, many challenges remain in the prevention and treatment of tuberculosis. Therefore, the development of safe and effective tuberculosis vaccines is an urgent issue. In this study, we identified cytotoxic T lymphocyte epitopes on drug resistance-associated membrane protein efflux pumps of MTB, the ATP-binding cassette and the major facilitator superfamilies. First, three online software were used to predict HLA-A2-restricted epitopes. Then, the candidate epitopes were confirmed with the T2A2 cell binding affinity and peptide/MHC (pMHC) complex stability assays and in vitro immune activity experiments. Two drug-resistant T lymphocyte epitopes, designated Rv1218c-p24 and Rv2477c-p182, were selected, and their immunogenic activities studied in vivo in genetically engineered mice. The immune activities of these two epitopes were improved with the help of complete Freund's adjuvant (CFA). The epitopes identified here provide a foundation for the diagnosis and treatment of patients infected with drug resistant and the future development of a multiepitope vaccine.
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影响因子：
4
作者：
Dos Santos SC;Teixeira MC;Dias PJ;Sá-Correia I
通讯作者：
Sá-Correia I
影响因子：
2.6
作者：
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通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
Behr, Marcel A.
影响因子：
5.1
作者：
Jin, Xing-Wei;Liu, Bo-Ke;Shao, Yuan
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Qi, Yuanming