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

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 i...

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Main Authors: 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
Format: article
Language:EN
Published: Public Library of Science (PLoS) 2013
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Online Access:https://doaj.org/article/7d339e7bda6e43eab95b487bd676cd5b
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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.