title: Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis.
abstract: The dormancy (DosR) regulon of Mycobacterium tuberculosis is expressed in vitro during hypoxia and low-dose nitric oxide stimulation. Tubercle bacilli are thought to encounter these conditions in humans during latent infection. In this study, immune responses were evaluated to 25 most strongly induced DosR-regulon-encoded proteins, referred to as latency antigens. Proliferation assays were performed using M. tuberculosis-specific T-cell lines and peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients, tuberculin skin test positive (TST+) individuals and uninfected controls. All 25 latency antigens were able to induce production of interferon-gamma (IFN-gamma) by T-cell lines. Eighteen latency antigens were also recognized by PBMC of M. tuberculosis-infected individuals, which indicates expression of the DosR-regulon during natural infection. Differential analysis showed that TST+ individuals recognized more latency antigens and with a stronger cumulative IFN-gamma response than TB patients, while the opposite profile was found for culture filtrate protein-10. In particular Rv1733c, Rv2029c, Rv2627c and Rv2628 induced strong IFN-gamma responses in TST+ individuals, with 61%, 61%, 52% and 35% responders, respectively. In conclusion, several new M. tuberculosis antigens were identified within the DosR-regulon. Particularly strong IFN-gamma responses to latency antigens were observed in latently infected individuals, suggesting that immune responses against these antigens may contribute to controlling latent M. tuberculosis infection.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eliane M S
authors.initials: EM
authors.lastname: Leyten
authors.forename: May Young
authors.initials: MY
authors.lastname: Lin
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Annemieke H
authors.initials: AH
authors.lastname: Friggen
authors.forename: Corine
authors.initials: C
authors.lastname: Prins
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Martin I
authors.initials: MI
authors.lastname: Voskuil
authors.forename: Karin
authors.initials: K
authors.lastname: Weldingh
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schoolnik
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Arend
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Michèl R
authors.initials: MR
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D018085:Regulon; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C000589489:Rv1733c protein, Mycobacterium tuberculosis; D007371:Interferon-gamma