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, Z Sebestyen, Jürgen Kuball, Alexandre M J J Bonvin, Tanja D de Gruijl, Hans J van der Vliet

Research output: Contribution to journalArticleAcademicpeer-review


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
Issue number1
Publication statusPublished - 1 Jan 2017


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