Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele

• Published in: Microbial pathogenesis 2012-09, Vol.53 (3-4), p.162-167
• Main Authors: Wang, Yan, Sun, Meiyi, He, Min, Cui, Honglian, Zhang, Junxian, Shi, Limin, Wang, Wei, Xu, Wenjiong, Gao, Bin, Ding, Jie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; alleles; Amino Acid Sequence; Asians; Bacteriology; Biological and medical sciences; cell-mediated immunity; Cells, Cultured; culture filtrates; Cytokines - immunology; cytotoxic T-lymphocytes; Epitope; epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; ESAT-6; Female; Fundamental and applied biological sciences. Psychology; Genes, MHC Class I; HLA antigens; HLA-A24; HLA-A24 Antigen - genetics; HLA-A24 Antigen - immunology; Humans; immunotherapy; in vitro studies; Leukocytes, Mononuclear - immunology; major histocompatibility complex; Male; Microbiology; Middle Aged; Miscellaneous; Molecular Sequence Data; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - isolation & purification; patients; peptides; Species Specificity; tuberculosis; Tuberculosis - genetics; Tuberculosis - immunology; Tuberculosis - microbiology; vaccine development; Young Adult
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2012.07.002

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. ► We study a panel of Mtb-derived peptides to identify binders for HLA-A24. ► Peptide P5 significantly elicits IFN-producing CTLs from HLA-A24+ TB donors. ► Peptide P5 is a weak binder for HLA-A24 molecule in a mini refolding assay. ► The identified epitope may be useful for immunotherapy and vaccine development.