Facoltà di scienze biomediche

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

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

In: Plos pathogens, 2013, vol. 9, no. 1, p. e1003130

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... More

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    Summary
    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.