Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele.
Microb Pathog
; 53(3-4): 162-7, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22819798
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Epitopos de Linfócito T
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Antígeno HLA-A24
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Mycobacterium tuberculosis
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article