Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection

PLoS One. 2009;4(5):e5590. doi: 10.1371/journal.pone.0005590. Epub 2009 May 18.


Background: T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans.

Methodology/principal findings: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI.

Conclusions: Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / physiology
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology*
  • Young Adult


  • Antigens, Bacterial