{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:24:50Z","timestamp":1788585890512,"version":"build-2803163510"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We analyzed whole genome\u2013based transcriptional profiles of Mycobacterium tuberculosis subjected to prolonged hypoxia to guide the discovery of novel potential Ags, by a combined bioinformatic and empirical approach. We analyzed the fold induction of the 100 most highly induced genes at 7 d of hypoxia, as well as transcript abundance, peptide-binding prediction (ProPred) adjusted for population-specific MHC class II allele frequency, and by literature search. Twenty-six candidate genes were selected by this bioinformatic approach and evaluated empirically using IFN-\u03b3 and IL-2 ELISPOT using immunodominant Ags (Acr-1, CFP-10, ESAT-6) as references. Twenty-three of twenty-six proteins induced an IFN-\u03b3 response in PBMCs of persons with active or latent tuberculosis. Five novel immunodominant proteins\u2014Rv1957, Rv1954c, Rv1955, Rv2022c, and Rv1471\u2014were identified that induced responses similar to CFP-10 and ESAT-6 in both magnitude and frequency. IL-2 responses were of lower magnitude than were those of IFN-\u03b3. Only moderate evidence of infection stage\u2013specific recognition of Ags was observed. Reconciliation of bioinformatic and empirical hierarchies of immunodominance revealed that Ags could be predicted, providing transcriptomic data were combined with peptide-binding prediction adjusted by population-specific MHC class II allele frequency.<\/jats:p>","DOI":"10.4049\/jimmunol.1202281","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T06:00:20Z","timestamp":1353391220000},"page":"5867-5876","source":"Crossref","is-referenced-by-count":27,"title":["Bioinformatic and Empirical Analysis of Novel Hypoxia-Inducible Targets of the Human Antituberculosis T Cell Response"],"prefix":"10.1093","volume":"189","author":[{"given":"Hannah P","family":"Gideon","sequence":"first","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin A","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Medical Research Council National Institute for Medical Research , London NW7 1AA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tige R","family":"Rustad","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolu","family":"Oni","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Department of Medicine, Imperial College London , London W2 1PG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinner","family":"Guio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London , London W2 1PG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Sherman","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Martin","family":"Vordermeier","sequence":"additional","affiliation":[{"name":"Veterinary Laboratories Agency , Weybridge KT15 3NB,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London , London W2 1PG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B","family":"Young","sequence":"additional","affiliation":[{"name":"Medical Research Council National Institute for Medical Research , London NW7 1AA,","place":["United Kingdom"]},{"name":"Department of Medicine, Imperial College London , London W2 1PG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town,","place":["South Africa"]},{"name":"Medical Research Council National Institute for Medical Research , London NW7 1AA,","place":["United Kingdom"]},{"name":"Department of Medicine, Imperial College London , London W2 1PG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,15]]},"reference":[{"key":"2025032409384057200_r1"},{"key":"2025032409384057200_r2","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/S0140-6736(07)61262-8","article-title":"Tuberculosis","volume":"370","author":"Maartens","year":"2007","journal-title":"Lancet"},{"key":"2025032409384057200_r3","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1099\/00221287-144-11-3195","article-title":"A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10)","volume":"144","author":"Berthet","year":"1998","journal-title":"Microbiology"},{"key":"2025032409384057200_r4","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1128\/iai.63.5.1710-1717.1995","article-title":"Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis","volume":"63","author":"S\u00f8rensen","year":"1995","journal-title":"Infect. 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