title: Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele.
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.
authors: Department of Microbiology, Nanjing Center for Disease Prevention and Control, Zizhulin 2, Nanjing 210003, China.
authors: Yan
authors: Y
authors: Wang
authors: Meiyi
authors: M
authors: Sun
authors: Min
authors: M
authors: He
authors: Honglian
authors: H
authors: Cui
authors: Junxian
authors: J
authors: Zhang
authors: Limin
authors: L
authors: Shi
authors: Wei
authors: W
authors: Wang
authors: Wenjiong
authors: W
authors: Xu
authors: Bin
authors: B
authors: Gao
authors: Jie
authors: J
authors: Ding
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013045:Species Specificity; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D059871:HLA-A24 Antigen