Journal article
Butyrophilin 3A1 Plays an Essential Role in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells
The Journal of immunology (1950), Vol.191(3), pp.1029-1042
08/01/2013
DOI: 10.4049/jimmunol.1300658
PMCID: PMC3884521
PMID: 23833237
Abstract
Most human γδ T cells express Vγ2Vδ2 TCRs and play important roles in microbial and tumor immunity. Vγ2Vδ2 T cells are stimulated by self- and foreign prenyl pyrophosphate intermediates in isoprenoid synthesis. However, little is known about the molecular basis for this stimulation. We find that a mAb specific for butyrophilin 3 (BTN3)/CD277 immunoglobulin superfamily proteins mimics prenyl pyrophosphates. The 20.1 mAb stimulated Vγ2Vδ2 T cell clones regardless of their functional phenotype or developmental origin, and selectively expanded blood Vγ2Vδ2 T cells. The γδ TCR mediates 20.1 mAb stimulation because IL-2 is released by β
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Jurkat cells transfected with Vγ2Vδ2 TCRs. 20.1 stimulation was not due to isopentenyl pyrophosphate (IPP) accumulation because 20.1 treatment of APC did not increase IPP levels. In addition, stimulation was not inhibited by statin treatment, which blocks IPP production. Importantly, small interfering RNA knockdown of BTN3A1 abolished stimulation by IPP that could be restored by re-expression of BTN3A1 but not by BTN3A2 or BTN3A3. Rhesus monkey and baboon APC presented HMBPP and 20.1 to human Vγ2Vδ2 T cells despite amino acid differences in BTN3A1 that localize to its outer surface. This suggests that the conserved inner and/or top surfaces of BTN3A1 interact with its counterreceptor. Although no binding site exists on the BTN3A1 extracellular domains, a model of the intracellular B30.2 domain predicts a basic pocket on its binding surface. However, BTN3A1 did not preferentially bind a photoaffinity prenyl pyrophosphate. Thus, BTN3A1 is required for stimulation by prenyl pyrophosphates but does not bind the intermediates with high affinity.
Details
- Title: Subtitle
- Butyrophilin 3A1 Plays an Essential Role in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells
- Creators
- Hong Wang - Division of Immunology, Department of Internal Medicine, Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242Olivier Henry - Department of Chemistry, University of Minnesota, Minneapolis, MN 55455Mark D Distefano - Department of Chemistry, University of Minnesota, Minneapolis, MN 55455Yen-Chih Wang - Department of Chemistry, University of Minnesota, Minneapolis, MN 55455Johanna Räikkönen - School of Pharmacy, University of Eastern Finland, Kuopio, Finland 70211Jukka Mönkkönen - School of Pharmacy, University of Eastern Finland, Kuopio, Finland 70211Yoshimasa Tanaka - Center for Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanCraig T Morita - Division of Immunology, Department of Internal Medicine, Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.191(3), pp.1029-1042
- DOI
- 10.4049/jimmunol.1300658
- PMID
- 23833237
- PMCID
- PMC3884521
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AR045504 || AR / National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS R01 GM058842 || GM / National Institute of General Medical Sciences : NIGMS U54 AI057160 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID P50 CA097274 || CA / National Cancer Institute : NCI
- Language
- English
- Date published
- 08/01/2013
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094219002771
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