Butyrophilin 3A1 engages the CDR2δ loop of the Vγ9Vδ2+ T cell receptor

Fulford, TS; Rigau, M; Yang, JZ; Ruan, Z; Singgih, KC; Soliman, C; Redmond, SJ; Zhang, T; Koay, HF; Ma, X; Zhang, Y; Gherardin, NA; Godfrey, DI; Uldrich, AP

Author(s): Fulford, TS; Rigau, M; Yang, JZ; Ruan, Z; Singgih, KC; Soliman, C; Redmond, SJ; Zhang, T; Koay, HF; Ma, X; Zhang, Y; Gherardin, NA; Godfrey, DI; Uldrich, AP;
Details: Publication Year 2026-09-08,Volume 45,Issue #9,Page 117912
Journal Title: Cell Reports
Publication Type: Research article
Abstract: Phosphoantigen (pAg) recognition by Vγ9Vδ2(+) T cells plays a critical role in immunity to pathogens and cancer. The butyrophilin (BTN) family of molecules have emerged as key regulators of γδ T cells; however, the underlying mechanisms remain unclear. Here, we demonstrate an interaction between BTN3A1 and Vγ9Vδ2(+) T cell receptor (TCR) in a cell-free assay, confirming that BTN3A1 is a direct ligand for the Vγ9Vδ2(+) TCR. Furthermore, immobilized recombinant BTN2A1 plus BTN3A1 extracellular domains are sufficient to activate Vδ2(+) T cells. Finally, we show that intracellular pAg accumulation can modulate binding of Vγ9Vδ2(+) TCR in a BTN3A1-dependent manner, indicating the important role of TCR binding to BTN3A1 in pAg recognition. These data confirm that BTN3A1, in conjunction with BTN2A1, is a direct ligand for Vγ9Vδ2(+) TCR, providing the key interactions required for pAg recognition.
Publisher: Cell Press
Keywords: CP: immunology; V gamma 9 V delta 2 T cell; butyrophilin 3A1; complementary-determining region 2 delta; gamma delta T cell receptor
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.celrep.2026.117912
Open Access at Publisher's Site: https://doi.org/10.1016/j.celrep.2026.117912
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-10-28 06:10:08

Last Modified: 2026-10-28 06:10:23