Journal article
Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells
International immunology, Vol.19(5), pp.657-673
05/2007
DOI: 10.1093/intimm/dxm031
PMID: 17446209
Abstract
Human Vγ2Vδ2 T cells are stimulated by prenyl pyrophosphates, such as isopentenyl pyrophosphate (IPP), and play important roles in mediating immunity against microbial pathogens and have potent anti-tumor activity. (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) has been identified as a metabolite in the 2-C-methyl-D-erythritol-4 phosphate (MEP) pathway for isoprenoid biosynthesis that is used by many bacteria and protozoan parasites. We find that HMBPP is the major Vγ2Vδ2 T-cell antigen for many bacteria, including Mycobacterium tuberculosis, Yersinia enterocolitica and Escherichia coli. HMBPP was a 30 000-fold more potent antigen than IPP. Using mutant bacteria, we show that bacterial antigen levels for Vγ2Vδ2 T cells are controlled by MEP pathway enzymes and find no evidence for the production of 3-formyl-1-butyl pyrophosphate. Moreover, HMBPP reactivity required only germ line-encoded Vγ2Vδ2 TCR elements and is present at birth. Importantly, we show that bacterial HMBPP levels correlated with their ability to expand Vγ2Vδ2 T cells in vivo upon engraftment into severe combined immunodeficiency-beige mice. Thus, the production of HMBPP by a microbial-specific isoprenoid pathway plays a major role in determining whether bacteria will stimulate Vγ2Vδ2 T cells in vivo. This preferential stimulation by a common microbial isoprenoid metabolite allows Vγ2Vδ2 T cells to respond to a broad array of pathogens using this pathway.
Details
- Title: Subtitle
- Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells
- Creators
- Kia-Joo Puan - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAChenggang Jin - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAHong Wang - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAGhanashyam Sarikonda - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAAmy M Raker - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAHoi K Lee - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAMegan I Samuelson - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USAElisabeth Märker-Hermann - 2Division of Rheumatology, Immunology and Nephrology, Department of Internal Medicine IV, Dr. Horst Schmidt Kliniken GmbH, 65191 Wiesbaden, GermanyLjiljana Pasa-Tolic - 3Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USAEdward Nieves - 4Laboratory for Molecular Analysis and Proteomics, Albert Einstein College of Medicine, Bronx, NY 10461, USAJosé-Luis Giner - 5Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, USATomohisa Kuzuyama - 6Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, JapanCraig T Morita - 1Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- International immunology, Vol.19(5), pp.657-673
- DOI
- 10.1093/intimm/dxm031
- PMID
- 17446209
- NLM abbreviation
- Int Immunol
- ISSN
- 0953-8178
- eISSN
- 1460-2377
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 05/2007
- Academic Unit
- Pathology; Immunology; Internal Medicine
- Record Identifier
- 9984047705902771
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