PLoS Pathogens (Jan 2013)

Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset.

  • Cecilia S Lindestam Arlehamn,
  • Anna Gerasimova,
  • Federico Mele,
  • Ryan Henderson,
  • Justine Swann,
  • Jason A Greenbaum,
  • Yohan Kim,
  • John Sidney,
  • Eddie A James,
  • Randy Taplitz,
  • Denise M McKinney,
  • William W Kwok,
  • Howard Grey,
  • Federica Sallusto,
  • Bjoern Peters,
  • Alessandro Sette

DOI
https://doi.org/10.1371/journal.ppat.1003130
Journal volume & issue
Vol. 9, no. 1
p. e1003130

Abstract

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An understanding of the immunological footprint of Mycobacterium tuberculosis (MTB) CD4 T cell recognition is still incomplete. Here we report that human Th1 cells specific for MTB are largely contained in a CXCR3(+)CCR6(+) memory subset and highly focused on three broadly immunodominant antigenic islands, all related to bacterial secretion systems. Our results refute the notion that secreted antigens act as a decoy, since both secreted proteins and proteins comprising the secretion system itself are targeted by a fully functional T cell response. In addition, several novel T cell antigens were identified which can be of potential diagnostic use, or as vaccine antigens. These results underline the power of a truly unbiased, genome-wide, analysis of CD4 MTB recognition based on the combined use of epitope predictions, high throughput ELISPOT, and T cell libraries using PBMCs from individuals latently infected with MTB.