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

PLoS Pathog. 2013 Jan;9(1):e1003130. doi: 10.1371/journal.ppat.1003130. Epub 2013 Jan 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Genome, Bacterial
  • Genome-Wide Association Study
  • Host-Pathogen Interactions
  • Humans
  • Immunologic Memory*
  • Latent Tuberculosis / genetics
  • Latent Tuberculosis / immunology*
  • Middle Aged
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / metabolism*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Young Adult


  • CCR6 protein, human
  • CXCR3 protein, human
  • Receptors, CCR6
  • Receptors, CXCR3