Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset
| Autor: | Erin J. Adams, Thomas Herrmann, Cassie-Marie Peigné, Jianqiang Li, Alexandra Leger, Jukka Mönkkönen, Richard Breathnach, Sonia Netzer, Yves Guillaume, Marc Bonneville, Christelle Harly, Daniel Olive, Emmanuel Scotet, Jürgen Kuball, Steven Nedellec, Hannu Mönkkönen, Julie Déchanet-Merville |
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| Přispěvatelé: | Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Eastern Finland, Julius-Maximilians-Universität Würzburg (JMU), University Medical Center [Utrecht], University of Chicago, Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHRISTELLE, HARLY |
| Rok vydání: | 2012 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Immunology Receptors Antigen T-Cell Lymphocyte Activation Biochemistry Butyrophilin Antigen Antigens CD T-Lymphocyte Subsets Humans Immunologic Factors Protein Isoforms Antigens Enzyme Inhibitors Phosphorylation RNA Small Interfering Receptor Antibodies Blocking Cells Cultured Immunobiology Gene knockdown biology Butyrophilins HEK 293 cells Fluorescence recovery after photobleaching Antibodies Monoclonal Cell Biology Hematology Molecular biology Recombinant Proteins Cell biology Clone Cells [SDV] Life Sciences [q-bio] Protein Transport HEK293 Cells biology.protein Antibody Antibodies Immobilized Protein Processing Post-Translational Intracellular |
| Zdroj: | Blood Blood, 2012, 120 (11), pp.2269-2279. ⟨10.1182/blood-2012-05-430470⟩ |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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