Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers

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Abstract Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity, however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell receptor (γδTCR) in complex with BTN member 2A1 (BTN2A1) revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that BTN3A1 is a second γδTCR ligand, that co-engages γδTCR via binding to this accessible apical surface. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1–BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to engage γδTCR; indeed, either forced separation or locking together of BTN2A1 and BTN3A1 resulted in enhanced or abrogated γδTCR interaction, respectively. Our findings reveal a new paradigm in immune activation, whereby γδTCRs recognize dual epitopes on BTN2A1 and BTN3A1 complexes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.