| Specific requirements for Vgamma9Vdelta2 T cell stimulation by a natural adenylated phosphoantigen. | |
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MedLine Citation:
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PMID: 19710470 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human Vgamma9Vdelta2 T lymphocytes recognize phosphorylated alkyl Ags. Isopentenyl pyrophosphate (IPP) was previously proposed as the main Ag responsible for Vgamma9Vdelta2 T cell activation by cancer cells. However, triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester (ApppI), a metabolite in which the isopentenyl moiety is linked to ATP, was reported in cells activated with aminobisphosphonates. The contribution of this compound to tumor-stimulatory activity was thus examined. ApppI induces selective expansion of Vgamma9Vdelta2 T cells from PBMCs. In the absence of APCs, however, ApppI has little stimulatory activity on Vgamma9Vdelta2 T cells, and optimal activation with ApppI requires addition of a nucleotide pyrophosphatase releasing IPP plus AMP. Thus, ApppI has no intrinsic stimulatory activity. Nevertheless, stimulation by ApppI is strengthened by the presence of APCs. Moreover, in contrast to IPP, ApppI can be efficiently pulsed on dendritic cells as well as on nonprofessional APCs. Pulsed APCs display stable and phosphatase-resistant stimulatory activity, indicative of Ag modification. HPLC analysis of tumor cell extracts indicates that latent phosphoantigenic activity is stored intracellularly in the Vgamma9Vdelta2 cell-sensitive tumor Daudi and can be activated by a nucleotide pyrophosphatase activity. The presence of ApppI in Daudi cell extracts was demonstrated by mass spectrometry. Nucleotidic Ags such as ApppI are thus a storage form of phosphoantigen which may represent a major source of phosphoantigenic activity in tumor cells. The unique properties of ApppI may be important for the design of Ags used in anticancer immunotherapeutic protocols using Vgamma9Vdelta2 cells. |
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Authors:
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Pierre Vantourout; Jayati Mookerjee-Basu; Corinne Rolland; Frédéric Pont; Hélène Martin; Christian Davrinche; Laurent O Martinez; Bertrand Perret; Xavier Collet; Christian Périgaud; Suzanne Peyrottes; Eric Champagne |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-26 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 183 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-03 Completed Date: 2009-09-23 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3848-57 Citation Subset: AIM; IM |
Affiliation:
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Département Lipoprotéines et Médiateurs Lipidiques, INSERM, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul Sabatier, Toulouse, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Monophosphate Adenosine Triphosphate / analogs & derivatives*, immunology Antigen-Presenting Cells / immunology Cell Line, Tumor Cells, Cultured Diphosphonates Hemiterpenes / immunology Humans Lymphoma, B-Cell / immunology, pathology Organophosphorus Compounds / immunology* Receptors, Antigen, T-Cell, gamma-delta / immunology* T-Lymphocytes / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Diphosphonates; 0/Hemiterpenes; 0/Organophosphorus Compounds; 0/Receptors, Antigen, T-Cell, gamma-delta; 0/T-cell receptor Vdelta2, human; 0/T-cell receptor Vgamma9, human; 0/triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester; 358-71-4/isopentenyl pyrophosphate; 56-65-5/Adenosine Triphosphate; 61-19-8/Adenosine Monophosphate |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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