Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers

Author:

Fulford Thomas S.,Soliman Caroline,Castle Rebecca G.,Rigau Marc,Ruan Zheng,Dolezal Olan,Seneviratna Rebecca,Brown Hamish G.,Hanssen Eric,Hammet Andrew,Li Shihan,Redmond Samuel J.,Chung Amy,Gorman Michael A.,Parker Michael W.,Patel Onisha,Peat Thomas S.,Newman Janet,Behren Andreas,Gherardin Nicholas A.,Godfrey Dale I.,Uldrich Adam P.

Abstract

AbstractButyrophilin (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.

Publisher

Cold Spring Harbor Laboratory

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