BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells - Archive ouverte HAL Access content directly
Journal Articles Cell Reports Year : 2021

BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells

(1) , (1) , (1) , (1) , (1) , (1) , (1) , (1) , (2, 3) , (2, 1, 3) , (4) , (5) , (5) , (6) , (5) , (5) , (5, 6)
1
2
3
4
5
6
Christine Pasero
Aude de Gassart
Norbert Vey

Abstract

The anti-tumor response of Vγ9Vδ2 T cells requires the sensing of accumulated phosphoantigens (pAgs) bound intracellularly to butyrophilin 3A1 (BTN3A1). In this study, we show that butyrophilin 2A1 (BTN2A1) is required for BTN3A-mediated Vγ9Vδ2 T cell cytotoxicity against cancer cells, and that expression of the BTN2A1/BTN3A1 complex is sufficient to trigger Vγ9Vδ2 TCR activation. Also, BTN2A1 interacts with all isoforms of BTN3A (BTN3A1, BTN3A2, BTN3A3), which appears to be a rate-limiting factor to BTN2A1 export to the plasma membrane. BTN2A1/BTN3A1 interaction is enhanced by pAgs and, strikingly, B30.2 domains of both proteins are required for pAg responsiveness. BTN2A1 expression in cancer cells correlates with bisphosphonate-induced Vγ9Vδ2 T cell cytotoxicity. Vγ9Vδ2 T cell killing of cancer cells is modulated by anti-BTN2A1 monoclonal antibodies (mAbs), whose action relies on the inhibition of BTN2A1 binding to the Vγ9Vδ2TCR. This demonstrates the potential of BTN2A1 as a therapeutic target and adds to the emerging butyrophilin-family cooperation pathway in γδ T cell activation.
Fichier principal
Vignette du fichier
PIIS2211124721007579.pdf (4.1 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

inserm-03547155 , version 1 (28-01-2022)

Identifiers

Cite

Carla Cano, Christine Pasero, Aude de Gassart, Clement Kerneur, Mélanie Gabriac, et al.. BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells. Cell Reports, 2021, 36 (2), pp.109359. ⟨10.1016/j.celrep.2021.109359⟩. ⟨inserm-03547155⟩
36 View
39 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More