Document Detail

Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines.
MedLine Citation:
PMID:  21203487     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-23
Journal Detail:
Title:  PLoS pathogens     Volume:  6     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2010  
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-05-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001237     Citation Subset:  IM    
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MeSH Terms
Anoxia / immunology*
Antigens, Bacterial / genetics,  immunology
BCG Vaccine / immunology
Gene Expression Profiling
Immunodominant Epitopes / biosynthesis,  genetics*
Immunologic Memory
T-Cell Antigen Receptor Specificity
T-Lymphocytes / immunology*
Transcriptional Activation*
Tuberculosis / immunology*
Grant Support
072070//Wellcome Trust; 072070//Wellcome Trust; 081667//Wellcome Trust; 084323//Wellcome Trust; 084323//Wellcome Trust; 088316//Wellcome Trust; 088316//Wellcome Trust; 37882//Wellcome Trust; MC_U117581288//Medical Research Council; MC_U117588499//Medical Research Council; U117588499(88499)//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Antigens, Bacterial; 0/BCG Vaccine; 0/Immunodominant Epitopes

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