PMID- 22819798 OWN - NLM STAT- MEDLINE DCOM- 20130116 LR - 20231113 IS - 1096-1208 (Electronic) IS - 0882-4010 (Print) IS - 0882-4010 (Linking) VI - 53 IP - 3-4 DP - 2012 Sep TI - Weak binder for MHC molecule is a potent Mycobacterium tuberculosis-specific CTL epitope in the context of HLA-A24 allele. PG - 162-7 LID - 10.1016/j.micpath.2012.07.002 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Wang, Yan AU - Wang Y AD - Department of Microbiology, Nanjing Center for Disease Prevention and Control, Zizhulin 2, Nanjing 210003, China. FAU - Sun, Meiyi AU - Sun M FAU - He, Min AU - He M FAU - Cui, Honglian AU - Cui H FAU - Zhang, Junxian AU - Zhang J FAU - Shi, Limin AU - Shi L FAU - Wang, Wei AU - Wang W FAU - Xu, Wenjiong AU - Xu W FAU - Gao, Bin AU - Gao B FAU - Ding, Jie AU - Ding J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120720 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Cytokines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A24 Antigen) SB - IM EIN - Microb Pathog. 2013 Mar;56:60 MH - Adolescent MH - Adult MH - Amino Acid Sequence MH - Cells, Cultured MH - Cytokines/immunology MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - Female MH - Genes, MHC Class I MH - HLA-A24 Antigen/genetics/*immunology MH - Humans MH - Leukocytes, Mononuclear/immunology MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Mycobacterium tuberculosis/genetics/*immunology/isolation & purification MH - Species Specificity MH - Tuberculosis/genetics/*immunology/microbiology MH - Young Adult PMC - PMC7127545 EDAT- 2012/07/24 06:00 MHDA- 2013/01/17 06:00 PMCR- 2012/07/20 CRDT- 2012/07/24 06:00 PHST- 2012/04/24 00:00 [received] PHST- 2012/07/01 00:00 [revised] PHST- 2012/07/03 00:00 [accepted] PHST- 2012/07/24 06:00 [entrez] PHST- 2012/07/24 06:00 [pubmed] PHST- 2013/01/17 06:00 [medline] PHST- 2012/07/20 00:00 [pmc-release] AID - S0882-4010(12)00134-9 [pii] AID - 10.1016/j.micpath.2012.07.002 [doi] PST - ppublish SO - Microb Pathog. 2012 Sep;53(3-4):162-7. doi: 10.1016/j.micpath.2012.07.002. Epub 2012 Jul 20.