Back to Search
Start Over
Prevention of Vγ9Vδ2 T cell activation by a Vγ9Vδ2 TCR nanobody
- Source :
- The Journal of Immunology, De Bruin, R C G, Stam, A G M, Vangone, A, Van Bergen En Henegouwen, P M P, Verheul, H M W, Sebestyén, Z, Kuball, J, Bonvin, A M J J, De Gruijl, T D & Van Der Vliet, H J 2017, ' Prevention of Vγ9Vδ2 T cell activation by a Vγ9Vδ2 TCR nanobody ', Journal of Immunology, vol. 198, no. 1, pp. 308-317 . https://doi.org/10.4049/jimmunol.1600948, Journal of Immunology, 198, 308. American Association of Immunologists, Journal of Immunology, 198(1), 308. American Association of Immunologists, Journal of Immunology, 198(1), 308-317. American Association of Immunologists
- Publication Year :
- 2017
-
Abstract
- Vγ9Vδ2 T cell activation plays an important role in antitumor and antimicrobial immune responses. However, there are conditions in which Vγ9Vδ2 T cell activation can be considered inappropriate for the host. Patients treated with aminobisphosphonates for hypercalcemia or metastatic bone disease often present with a debilitating acute phase response as a result of Vγ9Vδ2 T cell activation. To date, no agents are available that can clinically inhibit Vγ9Vδ2 T cell activation. In this study, we describe the identification of a single domain Ab fragment directed to the TCR of Vγ9Vδ2 T cells with neutralizing properties. This variable domain of an H chain–only Ab (VHH or nanobody) significantly inhibited both phosphoantigen-dependent and -independent activation of Vγ9Vδ2 T cells and, importantly, strongly reduced the production of inflammatory cytokines upon stimulation with aminobisphosphonate-treated cells. Additionally, in silico modeling suggests that the neutralizing VHH binds the same residues on the Vγ9Vδ2 TCR as the Vγ9Vδ2 T cell Ag-presenting transmembrane protein butyrophilin 3A1, providing information on critical residues involved in this interaction. The neutralizing Vγ9Vδ2 TCR VHH identified in this study might provide a novel approach to inhibit the unintentional Vγ9Vδ2 T cell activation as a consequence of aminobisphosphonate administration.
- Subjects :
- 0301 basic medicine
T cell
Immunology
Biology
Lymphocyte Activation
Proinflammatory cytokine
Cell Line
03 medical and health sciences
Immune system
Antigen
T-Lymphocyte Subsets
Journal Article
medicine
Immunology and Allergy
Cytotoxic T cell
Humans
T-cell receptor
Models, Immunological
Receptors, Antigen, T-Cell, gamma-delta
Flow Cytometry
Molecular biology
Antibodies, Neutralizing
3. Good health
Cell biology
Molecular Docking Simulation
030104 developmental biology
medicine.anatomical_structure
Cell culture
CD8
Single-Chain Antibodies
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 198
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology
- Accession number :
- edsair.doi.dedup.....e78d4c68387fcdb0449f672f2ca3202d