Memory T cells in latent mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset
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Lindestam Arlehamn, Cecilia S.
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Gerasimova, Anna
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Mele, Federico
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Henderson, Ryan
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Swann, Justine
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Greenbaum, Jason A.
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Kim, Yohan
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Sidney, John
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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James, Eddie A.
Benaroya Research Institute, Seattle, Washington, United States of America
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Taplitz, Randy
Antiviral Research Centre, University of California, San Diego, San Diego, California, United States of America
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McKinney, Denise M.
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Kwok, William W.
Benaroya Research Institute, Seattle, Washington, United States of America
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Grey, Howard
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Sallusto, Federica
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Peters, Bjoern
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Sette, Alessandro
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America
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Published in:
- 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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Medicine
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https://n2t.net/ark:/12658/srd1319175
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