Related Experiment Video

Updated: Aug 12, 2026

Expansion of Human Peripheral Blood γδ T Cells using Zoledronate
13:08

Expansion of Human Peripheral Blood γδ T Cells using Zoledronate

Published on: September 9, 2011

Phosphoantigen-driven dissociation of butyrophilin oligomers activates γδ T cells

Weizhi Xin1,2,3,4, Bangdong Huang1,2,3,4, Weijie Gao2,3,4

  • 1Fudan University, Shanghai, China.

Cell Discovery
|August 10, 2026
PubMed

γδ T cells represent a promising avenue for cancer immunotherapy. The Vγ9Vδ2 T-cell receptor (TCR), which is expressed by the predominant subset of γδ T cells, responds to phosphoantigen (pAg)-engaged butyrophilins (BTNs) on various cancer cells. However, the molecular mechanism underlying the pAg-mediated activation of Vγ9Vδ2 TCRs remains a subject of debate. Here, we employed an integrative approach to elucidate the mechanism of pAg reactivity in Vγ9Vδ2 T cells. Our results demonstrate that BTNs form higher-order oligomers in the absence of pAg. Upon pAg binding, these higher-order oligomers dissociate into separate tetramers, enabling Vγ9Vδ2 TCR engagement. This pAg-induced dissociation of higher-order BTN oligomers is critical for pAg-mediated activation of γδ T cells. Our findings reveal a mechanism of BTN higher-order oligomer dissociation-driven pAg sensing, providing valuable insight for future immunotherapeutic strategies.

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