Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis

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 immunodeficie...

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Main Authors: Yan Lin, Yu Dong, Yanfeng Gao, Ranran Shi, Yubing Li, Xiuman Zhou, Wenwen Liu, Guodong Li, Yuanming Qi, Yahong Wu
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/8899674
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author Yan Lin
Yu Dong
Yanfeng Gao
Ranran Shi
Yubing Li
Xiuman Zhou
Wenwen Liu
Guodong Li
Yuanming Qi
Yahong Wu
author_facet Yan Lin
Yu Dong
Yanfeng Gao
Ranran Shi
Yubing Li
Xiuman Zhou
Wenwen Liu
Guodong Li
Yuanming Qi
Yahong Wu
author_sort Yan Lin
collection DOAJ
description 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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institution Kabale University
issn 2314-8861
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publishDate 2021-01-01
publisher Wiley
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series Journal of Immunology Research
spelling doaj-art-4a4070bd48ec427182c7ef1cfb470d512025-02-03T01:28:29ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/88996748899674Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosisYan Lin0Yu Dong1Yanfeng Gao2Ranran Shi3Yubing Li4Xiuman Zhou5Wenwen Liu6Guodong Li7Yuanming Qi8Yahong Wu9School of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaTuberculosis 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.http://dx.doi.org/10.1155/2021/8899674
spellingShingle Yan Lin
Yu Dong
Yanfeng Gao
Ranran Shi
Yubing Li
Xiuman Zhou
Wenwen Liu
Guodong Li
Yuanming Qi
Yahong Wu
Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
Journal of Immunology Research
title Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
title_full Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
title_fullStr Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
title_full_unstemmed Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
title_short Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis
title_sort identification of ctl epitopes on efflux pumps of the atp binding cassette and the major facilitator superfamily of mycobacterium tuberculosis
url http://dx.doi.org/10.1155/2021/8899674
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