Journal
CELL HOST & MICROBE
Volume 18, Issue 5, Pages 538-548Publisher
CELL PRESS
DOI: 10.1016/j.chom.2015.10.008
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Funding
- National Institutes of Health [R01 AI090928, HHSN266200700022C]
- Swiss National Science Foundation [PP00P3_150750]
- Potts Memorial Foundation
- Belgian American Educational Foundation
- Swiss National Science Foundation (SNF) [PP00P3_150750] Funding Source: Swiss National Science Foundation (SNF)
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Pathogens that evade adaptive immunity typically exhibit antigenic variation. By contrast, it appears that although the chronic human tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis needs to counter host T cell responses, its T cell epitopes are hyperconserved. Here we present an extensive analysis of the T cell epitopes of M. tuberculosis. We combined population genomics with experimental immunology to determine the number and identity of T cell epitope sequence variants in 216 phylogenetically diverse strains of M. tuberculosis. Antigen conservation is indeed a hallmark of M. tuberculosis. However, our analysis revealed a set of seven variable antigens that were immunogenic in subjects with active TB. These findings suggest that M. tuberculosis uses mechanisms other than antigenic variation to evade T cells. T cell epitopes that exhibit sequence variation may not be subject to the same evasion mechanisms, and hence vaccines that include such variable epitopes may be more efficacious.
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