Cargando…
Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis CD8(+) T cell epitopes
New vaccines are needed to combat Mycobacterium tuberculosis (MTB) infections. The currently employed Bacillus Calmette‐Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug‐resistant tuberculosis (MDR‐TB) strains and the reduced immune capacity in cases of HIV coinfectio...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988290/ https://www.ncbi.nlm.nih.gov/pubmed/27072810 http://dx.doi.org/10.1111/jcmm.12867 |
_version_ | 1782448415064457216 |
---|---|
author | Liu, Su‐Dong Su, Jin Zhang, Shi‐Meng Dong, Hai‐Ping Wang, Hui Luo, Wei Wen, Qian He, Jian‐Chun Yang, Xiao‐Fan Ma, Li |
author_facet | Liu, Su‐Dong Su, Jin Zhang, Shi‐Meng Dong, Hai‐Ping Wang, Hui Luo, Wei Wen, Qian He, Jian‐Chun Yang, Xiao‐Fan Ma, Li |
author_sort | Liu, Su‐Dong |
collection | PubMed |
description | New vaccines are needed to combat Mycobacterium tuberculosis (MTB) infections. The currently employed Bacillus Calmette‐Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug‐resistant tuberculosis (MDR‐TB) strains and the reduced immune capacity in cases of HIV coinfection. CD8(+) T cells play an important role in the protective immunity against MTB infections, and the identification of immunogenic CD8(+) T cell epitopes specific for MTB is essential for the design of peptide‐based vaccines. To identify CD8(+) T cell epitopes of MTB proteins, we screened a set of 94 MTB antigens for HLA class I A*11:01‐binding motifs. HLA‐A*11:01 is one of the most prevalent HLA molecules in Southeast Asians, and definition of T cell epitopes it can restrict would provide significant coverage for the Asian population. Peptides that bound with high affinity to purified HLA molecules were subsequently evaluated in functional assays to detect interferon‐γ release and CD8(+) T cell proliferation in active pulmonary TB patients. We identified six novel epitopes, each derived from a unique MTB antigen, which were recognized by CD8(+) T cells from active pulmonary TB patients. In addition, a significant level of epitope‐specific T cells could be detected ex vivo in peripheral blood mononuclear cells from active TB patients by an HLA‐A*11:01 dextramer carrying the peptide Rv3130c(194‐204) (from the MTB triacylglycerol synthase Tgs1), which was the most frequently recognized epitope in our peptide library. In conclusion, this study identified six dominant CD8(+) T cell epitopes that may be considered potential targets for subunit vaccines or diagnostic strategies against TB. |
format | Online Article Text |
id | pubmed-4988290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49882902016-09-01 Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis CD8(+) T cell epitopes Liu, Su‐Dong Su, Jin Zhang, Shi‐Meng Dong, Hai‐Ping Wang, Hui Luo, Wei Wen, Qian He, Jian‐Chun Yang, Xiao‐Fan Ma, Li J Cell Mol Med Original Articles New vaccines are needed to combat Mycobacterium tuberculosis (MTB) infections. The currently employed Bacillus Calmette‐Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug‐resistant tuberculosis (MDR‐TB) strains and the reduced immune capacity in cases of HIV coinfection. CD8(+) T cells play an important role in the protective immunity against MTB infections, and the identification of immunogenic CD8(+) T cell epitopes specific for MTB is essential for the design of peptide‐based vaccines. To identify CD8(+) T cell epitopes of MTB proteins, we screened a set of 94 MTB antigens for HLA class I A*11:01‐binding motifs. HLA‐A*11:01 is one of the most prevalent HLA molecules in Southeast Asians, and definition of T cell epitopes it can restrict would provide significant coverage for the Asian population. Peptides that bound with high affinity to purified HLA molecules were subsequently evaluated in functional assays to detect interferon‐γ release and CD8(+) T cell proliferation in active pulmonary TB patients. We identified six novel epitopes, each derived from a unique MTB antigen, which were recognized by CD8(+) T cells from active pulmonary TB patients. In addition, a significant level of epitope‐specific T cells could be detected ex vivo in peripheral blood mononuclear cells from active TB patients by an HLA‐A*11:01 dextramer carrying the peptide Rv3130c(194‐204) (from the MTB triacylglycerol synthase Tgs1), which was the most frequently recognized epitope in our peptide library. In conclusion, this study identified six dominant CD8(+) T cell epitopes that may be considered potential targets for subunit vaccines or diagnostic strategies against TB. John Wiley and Sons Inc. 2016-04-12 2016-09 /pmc/articles/PMC4988290/ /pubmed/27072810 http://dx.doi.org/10.1111/jcmm.12867 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Liu, Su‐Dong Su, Jin Zhang, Shi‐Meng Dong, Hai‐Ping Wang, Hui Luo, Wei Wen, Qian He, Jian‐Chun Yang, Xiao‐Fan Ma, Li Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis CD8(+) T cell epitopes |
title | Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis
CD8(+) T cell epitopes |
title_full | Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis
CD8(+) T cell epitopes |
title_fullStr | Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis
CD8(+) T cell epitopes |
title_full_unstemmed | Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis
CD8(+) T cell epitopes |
title_short | Identification of HLA‐A*11:01‐restricted Mycobacterium tuberculosis
CD8(+) T cell epitopes |
title_sort | identification of hla‐a*11:01‐restricted mycobacterium tuberculosis
cd8(+) t cell epitopes |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988290/ https://www.ncbi.nlm.nih.gov/pubmed/27072810 http://dx.doi.org/10.1111/jcmm.12867 |
work_keys_str_mv | AT liusudong identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT sujin identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT zhangshimeng identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT donghaiping identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT wanghui identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT luowei identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT wenqian identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT hejianchun identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT yangxiaofan identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes AT mali identificationofhlaa1101restrictedmycobacteriumtuberculosiscd8tcellepitopes |