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Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines
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نویسنده
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gideon h.p. ,wilkinson k.a. ,rustad t.r. ,oni t. ,guio h. ,kozak r.a. ,sherman d.r. ,meintjes g. ,behr m.a. ,vordermeier h.m. ,young d.b. ,wilkinson r.j.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 12
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چکیده
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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.
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آدرس
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institute of infectious diseases and molecular medicine,university of cape town,observatory, South Africa, institute of infectious diseases and molecular medicine,university of cape town,observatory,south africa,mrc national institute for medical research,mill hill,london, United Kingdom, seattle biomedical research institute,seattle,washington, United States, institute of infectious diseases and molecular medicine,university of cape town,observatory,south africa,division of medicine and center for molecular microbiology and infection,imperial college london,london, United Kingdom, division of medicine and center for molecular microbiology and infection,imperial college london,london, United Kingdom, mcgill university health centre,montreal, Canada, seattle biomedical research institute,seattle,washington, United States, institute of infectious diseases and molecular medicine,university of cape town,observatory, South Africa, mcgill university health centre,montreal, Canada, veterinary laboratories agency,weybridge, United Kingdom, mrc national institute for medical research,mill hill,london,united kingdom,division of medicine and center for molecular microbiology and infection,imperial college london,london, United Kingdom, institute of infectious diseases and molecular medicine,university of cape town,observatory,south africa,mrc national institute for medical research,mill hill,london,united kingdom,division of medicine and center for molecular microbiology and infection,imperial college london,london, United Kingdom
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Authors
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