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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Bioinformatic and empirical analysis of novel hypoxia-inducible targets of the human antituberculosis T cell response
Journal of Immunology, Volume 189, No. 12, Year 2012
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Description
We analyzed whole genome-based 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-γ and IL-2 ELISPOT using immunodominant Ags (Acr-1, CFP-10, ESAT-6) as references. Twenty-three of twenty-six proteins induced an IFN-γ response in PBMCs of persons with active or latent tuberculosis. Five novel immunodominant proteins - Rv1957, Rv1954c, Rv1955, Rv2022c, and Rv1471 - were 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-γ. Only moderate evidence of infection stage-specific 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. Copyright © 2012 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Gideon, Hannah Priyadarshini
South Africa, Cape Town
University of Cape Town
Andrea Wilkinson, Katalin Andrea
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Mrc National Institute for Medical Research
Rustad, Tige R.
United States, Seattle
Seattle Biomedical Research Institute
Oni, Tolu
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Guio, H.
United Kingdom, London
Imperial College London
Sherman, David R.
United States, Seattle
Seattle Biomedical Research Institute
Vordermeier, Hans Martin
United Kingdom, Addlestone
Animal and Plant Health Agency
Robertson, Brian D.
United Kingdom, London
Imperial College London
Young, Douglas Brownlee
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Wilkinson, Robert J.
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College London
Statistics
Citations: 30
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.4049/jimmunol.1202281
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study