Prevention of Vγ9Vδ2 T Cell Activation by a Vγ9Vδ2 TCR Nanobody.
J Immunol
; 198(1): 308-317, 2017 01 01.
Article
en En
| MEDLINE
| ID: mdl-27895170
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.
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Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Subgrupos de Linfocitos T
/
Receptores de Antígenos de Linfocitos T gamma-delta
/
Anticuerpos de Cadena Única
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article