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. METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intrace...

Full description

Bibliographic Details
Main Authors: Sebastian D Schuck, Henrik Mueller, Frank Kunitz, Albert Neher, Harald Hoffmann, Kees L C M Franken, Dirk Repsilber, Tom H M Ottenhoff, Stefan H E Kaufmann, Marc Jacobsen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2680040?pdf=render
_version_ 1818765702324027392
author Sebastian D Schuck
Henrik Mueller
Frank Kunitz
Albert Neher
Harald Hoffmann
Kees L C M Franken
Dirk Repsilber
Tom H M Ottenhoff
Stefan H E Kaufmann
Marc Jacobsen
author_facet Sebastian D Schuck
Henrik Mueller
Frank Kunitz
Albert Neher
Harald Hoffmann
Kees L C M Franken
Dirk Repsilber
Tom H M Ottenhoff
Stefan H E Kaufmann
Marc Jacobsen
author_sort Sebastian D Schuck
collection DOAJ
description 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.
first_indexed 2024-12-18T08:22:17Z
format Article
id doaj.art-89c64a6f3f85446eb6ba1e2aa4faffe2
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-18T08:22:17Z
publishDate 2009-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-89c64a6f3f85446eb6ba1e2aa4faffe22022-12-21T21:14:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e559010.1371/journal.pone.0005590Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.Sebastian D SchuckHenrik MuellerFrank KunitzAlbert NeherHarald HoffmannKees L C M FrankenDirk RepsilberTom H M OttenhoffStefan H E KaufmannMarc JacobsenBACKGROUND: 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.http://europepmc.org/articles/PMC2680040?pdf=render
spellingShingle Sebastian D Schuck
Henrik Mueller
Frank Kunitz
Albert Neher
Harald Hoffmann
Kees L C M Franken
Dirk Repsilber
Tom H M Ottenhoff
Stefan H E Kaufmann
Marc Jacobsen
Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
PLoS ONE
title Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
title_full Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
title_fullStr Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
title_full_unstemmed Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
title_short Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.
title_sort identification of t cell antigens specific for latent mycobacterium tuberculosis infection
url http://europepmc.org/articles/PMC2680040?pdf=render
work_keys_str_mv AT sebastiandschuck identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT henrikmueller identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT frankkunitz identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT albertneher identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT haraldhoffmann identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT keeslcmfranken identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT dirkrepsilber identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT tomhmottenhoff identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT stefanhekaufmann identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection
AT marcjacobsen identificationoftcellantigensspecificforlatentmycobacteriumtuberculosisinfection