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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines
PLoS Pathogens, Volume 6, No. 12, Article e1001237, Year 2010
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Description
M. tuberculosis (MTB) species-specific antigenic determinants of the human T cell response are important for immunodiagnosis and vaccination. As hypoxia is a stimulus in chronic tuberculosis infection, we analyzed transcriptional profiles of MTB subject to 168 hours of hypoxia to test the hypothesis that upregulation by hypoxia might result in gene products being recognized as antigens. We identified upregulation of two region of difference (RD) 11 (Rv2658C and Rv2659c), and one RD2 (Rv1986) absent from commonly used BCG strains. In MTB infected persons, the IL-2 ELISpot response to Rv1986 peptides was several times greater than the corresponding IFN-c response to the reference immunodominant ESAT-6 or CFP-10 antigens. The IL-2 response was confined to two epitopic regions containing residues 61-80 and 161-180. The biggest population of IL-2 secreting T cells was single cytokine positive central memory T cells. The IL-2 response to live MTB bacilli lacking Rv1986 was significantly lower than the response to wild type or mutant complemented with Rv1986. In addition, the IL-2 response to Rv1986 was significantly lower in HIV-TB co-infected persons than in HIV uninfected persons, and significantly increased during antiretroviral therapy. These findings demonstrate that Rv1986 is an immunodominant target of memory T cells and is therefore of relevance when considering the partial efficacy of currently used BCG vaccines and provide evidence for a clinical trial comparing BCG strains. © 2010 Gideon et al.
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
Kozak, Robert
Canada, Montreal
Centre Universitaire de Santé Mcgill
Sherman, David R.
United States, Seattle
Seattle Biomedical Research Institute
Meintjes, Graeme Ayton
South Africa, Cape Town
University of Cape Town
Behr, Marcel A.
Canada, Montreal
Centre Universitaire de Santé Mcgill
Vordermeier, Hans Martin
United Kingdom, Addlestone
Animal and Plant Health Agency
Young, Douglas Brownlee
United Kingdom, London
Mrc National Institute for Medical Research
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: 40
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1371/journal.ppat.1001237
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study