Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
BACKGROUND
T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans.


RESULTS
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.
Schuck
Sebastian D
SD
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Mueller
Henrik
H
Kunitz
Frank
F
Neher
Albert
A
Hoffmann
Harald
H
Franken
Kees L C M
KL
Repsilber
Dirk
D
Ottenhoff
Tom H M
TH
Kaufmann
Stefan H E
SH
Jacobsen
Marc
M
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*; D055815:Young Adult
D000942:Antigens, Bacterial