title: Immunological responses and epitope mapping by tuberculosis-associated antigens within the RD1 region in Japanese patients.
abstract: Tuberculosis remains a major global health problem worldwide, and hence there is a need for novel vaccines that better induce cellular-mediated immunity (CMI). In search of a better vaccine target, the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and the interferon-γ ELISPOT assay (ELISPOT) were used to compare the magnitude of CMI in patients. Results of the ELISPOT assay led to the discovery of specific epitopes within the early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10) proteins. Both peptides showed a strong association with several HLA class II DRB1 molecules in the Japanese population. Using ESAT-6-specific HLA class II tetramers, we determined that the expression of ESAT-6-specific CD4+ lymphocytes was significantly decreased in treated patients compared with active patients. In addition, programmed death-1 (PD-1)/killer cell lectin-like receptor G1 (KLRG-1) double positive cells were found only in treated patients and not in those with active TB. These data could provide clues for the development of novel tuberculosis vaccines.
authors.affiliation: National Hospital Organization, Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagai
authors.affiliation: National Hospital Organization, Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan.
authors.forename: Maho
authors.identifier: 0000-0002-2265-1950
authors.initials: M
authors.lastname: Suzukawa
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba, Higashi-Murayama, Tokyo 189-0002, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: National Hospital Organization, Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Facultad de Medicina, Department of Microbiology I-Immunology, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba, Higashi-Murayama, Tokyo 189-0002, Japan.
authors.forename: Koichi
authors.identifier: 0000-0001-8659-4660
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba, Higashi-Murayama, Tokyo 189-0002, Japan.
authors.forename: Yoshihiko
authors.identifier: 0000-0002-3132-0715
authors.initials: Y
authors.lastname: Hoshino
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D007371:Interferon-gamma
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