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

doi:10.1371/journal.ppat.1003130

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Journal article

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. La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Gerasimova, Anna La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Mele, Federico Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Henderson, Ryan La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Swann, Justine La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Greenbaum, Jason A. La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Kim, Yohan La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Sidney, John La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
James, Eddie A. Benaroya Research Institute, Seattle, Washington, United States of America
Taplitz, Randy Antiviral Research Centre, University of California, San Diego, San Diego, California, United States of America
McKinney, Denise M. La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Kwok, William W. Benaroya Research Institute, Seattle, Washington, United States of America
Grey, Howard La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Peters, Bjoern La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
Sette, Alessandro La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America

24.01.2013

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Plos pathogens. - 2013, vol. 9, no. 1, p. e1003130

English 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.

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