6XLQ

Crystal Structure of the Human BTN3A1 Ectodomain in Complex with the CTX-2026 Fab

Summary for 6XLQ

• Entry DOI: 10.2210/pdb6xlq/pdb
• Descriptor: Butyrophilin subfamily 3 member A1, CTX-2026 Heavy Chain, CTX-2026 Light Chain, ... (4 entities in total)
• Functional Keywords: gamma/delta t cell activation alpha/beta t cell suppression, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 284699.26

Authors

Payne, K.K.,Mine, J.A.,Biswas, S.,Chaurio, R.A.,Perales-Puchalt, A.,Anadon, C.M.,Costich, T.L.,Harro, C.M.,Walrath, J.,Ming, Q.,Tcyganov, E.,Buras, A.L.,Rigolizzo, K.E.,Mandal, G.,Lajoie, J.,Ophir, M.,Tchou, J.,Marchion, D.,Luca, V.C.,Bobrowicz, P.,McLaughlin, B.,Eskiocak, U.,Schmidt, M.,Cubillos-Ruiz, J.R.,Rodriguez, P.C.,Gabrilovich, D.I.,Conejo-Garcia, J.R. (deposition date: 2020-06-29, release date: 2020-09-02, Last modification date: 2024-10-23)

Primary citation

Payne, K.K.,Mine, J.A.,Biswas, S.,Chaurio, R.A.,Perales-Puchalt, A.,Anadon, C.M.,Costich, T.L.,Harro, C.M.,Walrath, J.,Ming, Q.,Tcyganov, E.,Buras, A.L.,Rigolizzo, K.E.,Mandal, G.,Lajoie, J.,Ophir, M.,Tchou, J.,Marchion, D.,Luca, V.C.,Bobrowicz, P.,McLaughlin, B.,Eskiocak, U.,Schmidt, M.,Cubillos-Ruiz, J.R.,Rodriguez, P.C.,Gabrilovich, D.I.,Conejo-Garcia, J.R.
BTN3A1 governs antitumor responses by coordinating alpha beta and gamma delta T cells.
Science, 369:942-949, 2020

PubMed Abstract: Gamma delta (γδ) T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex-independent tumoricidal potential. Activation of γδ T cells can be elicited by butyrophilin and butyrophilin-like molecules that are structurally similar to the immunosuppressive B7 family members, yet how they regulate and coordinate αβ and γδ T cell responses remains unknown. Here, we report that the butyrophilin BTN3A1 inhibits tumor-reactive αβ T cell receptor activation by preventing segregation of N-glycosylated CD45 from the immune synapse. Notably, CD277-specific antibodies elicit coordinated restoration of αβ T cell effector activity and BTN2A1-dependent γδ lymphocyte cytotoxicity against BTN3A1 cancer cells, abrogating malignant progression. Targeting BTN3A1 therefore orchestrates cooperative killing of established tumors by αβ and γδ T cells and may present a treatment strategy for tumors resistant to existing immunotherapies.

PubMed: 32820120
DOI: 10.1126/science.aay2767

Experimental method

X-RAY DIFFRACTION (3 Å)