Cargando…
Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele
Tuberculosis causes serious health problem for the world population. Antigenic peptides selected by pathogen-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and HLA-A restricted responses may be of...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127545/ https://www.ncbi.nlm.nih.gov/pubmed/22819798 http://dx.doi.org/10.1016/j.micpath.2012.07.002 |
_version_ | 1783516383854723072 |
---|---|
author | Wang, Yan Sun, Meiyi He, Min Cui, Honglian Zhang, Junxian Shi, Limin Wang, Wei Xu, Wenjiong Gao, Bin Ding, Jie |
author_facet | Wang, Yan Sun, Meiyi He, Min Cui, Honglian Zhang, Junxian Shi, Limin Wang, Wei Xu, Wenjiong Gao, Bin Ding, Jie |
author_sort | Wang, Yan |
collection | PubMed |
description | Tuberculosis causes serious health problem for the world population. Antigenic peptides selected by pathogen-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and HLA-A restricted responses may be of interest for vaccine development and the understanding of cellular immunity. A series of peptides derived from the 10-KDa culture filtrate protein (CFP10) and the 6 kDa early secretory antigenic target (ESAT-6) in the Mycobacterium tuberculosis (Mtb) have been screened and a CTL epitope restricted by the human leukocyte antigen HLA-A24, a common HLA allele in Asian people, has been identified. In this study, we studied a panel of CFP10 and ESAT-6-derived peptides to identify those with binding motifs for HLA-A24 molecules. The antigenicity of candidate peptides was assessed with in vitro refolding tests and an enzyme-linked immunospot (ELISPOT) assay, and by tetramer staining to determine the capacity to stimulate CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A24-positive TB Patients. We report that one novel candidate peptide at positions 5–14 of ESAT-6 of Mtb could induce peptide-specific CTLs from PBMCs of HLA-A24-positive patients, but not from HLA-A24-negative patients and HLA-A24-positive healthy controls. Identified epitope is a weak binder for HLA-A24 molecule in a mini MHC refolding assay. Since the peptide is presented by a common HLA class I molecule, it may be useful for immunotherapy against Mtb infection and vaccine development in the large population of Mtb-infected patients. |
format | Online Article Text |
id | pubmed-7127545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71275452020-04-08 Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele Wang, Yan Sun, Meiyi He, Min Cui, Honglian Zhang, Junxian Shi, Limin Wang, Wei Xu, Wenjiong Gao, Bin Ding, Jie Microb Pathog Article Tuberculosis causes serious health problem for the world population. Antigenic peptides selected by pathogen-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and HLA-A restricted responses may be of interest for vaccine development and the understanding of cellular immunity. A series of peptides derived from the 10-KDa culture filtrate protein (CFP10) and the 6 kDa early secretory antigenic target (ESAT-6) in the Mycobacterium tuberculosis (Mtb) have been screened and a CTL epitope restricted by the human leukocyte antigen HLA-A24, a common HLA allele in Asian people, has been identified. In this study, we studied a panel of CFP10 and ESAT-6-derived peptides to identify those with binding motifs for HLA-A24 molecules. The antigenicity of candidate peptides was assessed with in vitro refolding tests and an enzyme-linked immunospot (ELISPOT) assay, and by tetramer staining to determine the capacity to stimulate CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A24-positive TB Patients. We report that one novel candidate peptide at positions 5–14 of ESAT-6 of Mtb could induce peptide-specific CTLs from PBMCs of HLA-A24-positive patients, but not from HLA-A24-negative patients and HLA-A24-positive healthy controls. Identified epitope is a weak binder for HLA-A24 molecule in a mini MHC refolding assay. Since the peptide is presented by a common HLA class I molecule, it may be useful for immunotherapy against Mtb infection and vaccine development in the large population of Mtb-infected patients. Elsevier Ltd. 2012 2012-07-20 /pmc/articles/PMC7127545/ /pubmed/22819798 http://dx.doi.org/10.1016/j.micpath.2012.07.002 Text en Copyright © 2012 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Wang, Yan Sun, Meiyi He, Min Cui, Honglian Zhang, Junxian Shi, Limin Wang, Wei Xu, Wenjiong Gao, Bin Ding, Jie Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title | Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title_full | Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title_fullStr | Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title_full_unstemmed | Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title_short | Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele |
title_sort | weak binder for mhc molecule is a potent mycobacterium tuberculosis-specific ctl epitope in the context of hla-a24 allele |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127545/ https://www.ncbi.nlm.nih.gov/pubmed/22819798 http://dx.doi.org/10.1016/j.micpath.2012.07.002 |
work_keys_str_mv | AT wangyan weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT sunmeiyi weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT hemin weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT cuihonglian weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT zhangjunxian weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT shilimin weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT wangwei weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT xuwenjiong weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT gaobin weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele AT dingjie weakbinderformhcmoleculeisapotentmycobacteriumtuberculosisspecificctlepitopeinthecontextofhlaa24allele |