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.

中文翻译：

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ATP结合盒和结核分枝杆菌主要促进子超家族外排泵上CTL表位的鉴定

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。随着耐药结核分枝杆菌数量的增加(MTB) 菌株和 MTB 与人类免疫缺陷病毒共感染的流行，结核病的预防和治疗仍然存在许多挑战。因此，开发安全有效的结核病疫苗是当务之急。在这项研究中，我们在 MTB、ATP 结合盒和主要促进剂超家族的耐药性相关膜蛋白外排泵上鉴定了细胞毒性 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，候选表位通过 T2A2 细胞结合亲和力和肽/MHC (pMHC) 复合物稳定性测定和体外确认免疫活性实验。选择了两个耐药性 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活性。在完全弗氏佐剂（CFA）的帮助下，这两个表位的免疫活性得到提高。这里鉴定的表位为耐药感染患者的诊断和治疗以及多表位疫苗的未来开发提供了基础。