| Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset. | |
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MedLine Citation:
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PMID: 22767497 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusceptible target cells with antibody 20.1 against CD277, a member of the extended B7 superfamily related to butyrophilin, mimics PAg-induced Vγ9Vδ2 T-cell activation and that the Vγ9Vδ2 T-cell receptor is implicated in this effect. Vγ9Vδ2 T-cell activation can be abrogated by exposing susceptible cells (tumor and mycobacteria-infected cells, or aminobisphosphonate-treated cells with up-regulated PAg levels) to antibody 103.2 against CD277. CD277 knockdown and domain-shuffling approaches confirm the key implication of the CD277 isoform BTN3A1 in PAg sensing by Vγ9Vδ2 T cells. Fluorescence recovery after photobleaching (FRAP) experiments support a causal link between intracellular PAg accumulation, decreased BTN3A1 membrane mobility, and ensuing Vγ9Vδ2 T-cell activation. This study demonstrates a novel role played by B7-like molecules in human γδ T-cell antigenic activation and paves the way for new strategies to improve the efficiency of immunotherapies using Vγ9Vδ2 T cells. |
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Authors:
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Christelle Harly; Yves Guillaume; Steven Nedellec; Cassie-Marie Peigné; Hannu Mönkkönen; Jukka Mönkkönen; Jianqiang Li; Jürgen Kuball; Erin J Adams; Sonia Netzer; Julie Déchanet-Merville; Alexandra Léger; Thomas Herrmann; Richard Breathnach; Daniel Olive; Marc Bonneville; Emmanuel Scotet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-07-05 |
Journal Detail:
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Title: Blood Volume: 120 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-14 Completed Date: 2012-12-03 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2269-79 Citation Subset: AIM; IM |
Affiliation:
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Inserm, U892, F-44000, Nantes, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Blocking Antibodies, Immobilized Antibodies, Monoclonal Antigens / metabolism* Antigens, CD / chemistry, genetics, metabolism* Cells, Cultured Clone Cells Enzyme Inhibitors / pharmacology HEK293 Cells Humans Immunologic Factors / pharmacology Lymphocyte Activation* / drug effects Phosphorylation / drug effects Protein Isoforms / agonists, antagonists & inhibitors, genetics, metabolism Protein Processing, Post-Translational / drug effects Protein Transport / drug effects RNA, Small Interfering Receptors, Antigen, T-Cell / agonists, antagonists & inhibitors, metabolism* Recombinant Proteins / agonists, antagonists & inhibitors, metabolism T-Lymphocyte Subsets / cytology, drug effects, immunology, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI073922/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Blocking; 0/Antibodies, Immobilized; 0/Antibodies, Monoclonal; 0/Antigens; 0/Antigens, CD; 0/BTN3A1 protein, human; 0/Enzyme Inhibitors; 0/Immunologic Factors; 0/Protein Isoforms; 0/RNA, Small Interfering; 0/Receptors, Antigen, T-Cell; 0/Recombinant Proteins |
| Comments/Corrections | |
Comment In:
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Blood. 2012 Sep 13;120(11):2159-61
[PMID:
22977080
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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