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 IFNγ 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. © 2009 Schuck et al.
CITATION STYLE
Schuck, S. D., Mueller, H., Kunitz, F., Neher, A., Hoffmann, H., Franken, K. L. C. M., … Jacobsen, M. (2009). Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection. PLoS ONE, 4(5). https://doi.org/10.1371/journal.pone.0005590
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