Human T-cell responses to 25 novel antigens encoded by genes of the dormancy regulon of Mycobacterium tuberculosis

Microbes Infect. 2006 Jul;8(8):2052-60. doi: 10.1016/j.micinf.2006.03.018. Epub 2006 Jun 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / physiology
  • Regulon
  • Statistics as Topic
  • T-Lymphocytes / immunology*
  • Tuberculin Test


  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • Rv1733c protein, Mycobacterium tuberculosis
  • Interferon-gamma