Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.

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...

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Autores principales:	Hannah Priyadarshini Gideon, Katalin Andrea Wilkinson, Tige R Rustad, Tolu Oni, Heinner Guio, Robert Andrew Kozak, David R Sherman, Graeme Meintjes, Marcel A Behr, Hans Martin Vordermeier, Douglas Brownlee Young, Robert John Wilkinson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5f7c112149f143e6abf37c61a78902fa
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spelling	oai:doaj.org-article:5f7c112149f143e6abf37c61a78902fa2021-11-18T06:03:42ZHypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.1553-73661553-737410.1371/journal.ppat.1001237https://doaj.org/article/5f7c112149f143e6abf37c61a78902fa2010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21203487/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374M. 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-γ 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.Hannah Priyadarshini GideonKatalin Andrea WilkinsonTige R RustadTolu OniHeinner GuioRobert Andrew KozakDavid R ShermanGraeme MeintjesMarcel A BehrHans Martin VordermeierDouglas Brownlee YoungRobert John WilkinsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 12, p e1001237 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Hannah Priyadarshini Gideon Katalin Andrea Wilkinson Tige R Rustad Tolu Oni Heinner Guio Robert Andrew Kozak David R Sherman Graeme Meintjes Marcel A Behr Hans Martin Vordermeier Douglas Brownlee Young Robert John Wilkinson Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
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-γ 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.
format	article
author	Hannah Priyadarshini Gideon Katalin Andrea Wilkinson Tige R Rustad Tolu Oni Heinner Guio Robert Andrew Kozak David R Sherman Graeme Meintjes Marcel A Behr Hans Martin Vordermeier Douglas Brownlee Young Robert John Wilkinson
author_facet	Hannah Priyadarshini Gideon Katalin Andrea Wilkinson Tige R Rustad Tolu Oni Heinner Guio Robert Andrew Kozak David R Sherman Graeme Meintjes Marcel A Behr Hans Martin Vordermeier Douglas Brownlee Young Robert John Wilkinson
author_sort	Hannah Priyadarshini Gideon
title	Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
title_short	Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
title_full	Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
title_fullStr	Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
title_full_unstemmed	Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
title_sort	hypoxia induces an immunodominant target of tuberculosis specific t cells absent from common bcg vaccines.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/5f7c112149f143e6abf37c61a78902fa
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Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.

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