Prevention of Vγ9Vδ2 T cell activation by a Vγ9Vδ2 TCR nanobody

Renée C.G. De Bruin, Anita G.M. Stam, Anna Vangone, Paul M.P. Van Bergen En Henegouwen, Henk M.W. Verheul, Zsolt Sebestyén, Jürgen Kuball, Alexandre M.J.J. Bonvin, Tanja D. De Gruijl, Hans J. Van Der Vliet*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)308-317
Number of pages10
JournalJournal of Immunology
Volume198
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

Cite this