Document Detail

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset.
MedLine Citation:
PMID:  22767497     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-05
Journal Detail:
Title:  Blood     Volume:  120     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2012-12-03     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2269-79     Citation Subset:  AIM; IM    
Inserm, U892, F-44000, Nantes, France.
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MeSH Terms
Antibodies, Blocking
Antibodies, Immobilized
Antibodies, Monoclonal
Antigens / metabolism*
Antigens, CD / chemistry,  genetics,  metabolism*
Cells, Cultured
Clone Cells
Enzyme Inhibitors / pharmacology
HEK293 Cells
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
Reg. No./Substance:
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
Comment In:
Blood. 2012 Sep 13;120(11):2159-61   [PMID:  22977080 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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