TY  - JOUR
A1  - Karunakaran, Mohindar M.
A1  - Subramanian, Hariharan
A1  - Jin, Yiming
A1  - Mohammed, Fiyaz
A1  - Kimmel, Brigitte
A1  - Juraske, Claudia
A1  - Starick, Lisa
A1  - Nöhren, Anna
A1  - Länder, Nora
A1  - Willcox, Carrie R.
A1  - Singh, Rohit
A1  - Schamel, Wolfgang W.
A1  - Nikolaev, Viacheslav O.
A1  - Kunzmann, Volker
A1  - Wiemer, Andrew J.
A1  - Willcox, Benjamin E.
A1  - Herrmann, Thomas
T1  - A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing
JF  - Nature Communications
N2  - Butyrophilin (BTN)–3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.
KW  - gammadelta T cells
KW  - immunosurveillance
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358179
VL  - 14
ER  -