6xlq
From Proteopedia
Crystal Structure of the Human BTN3A1 Ectodomain in Complex with the CTX-2026 Fab
Structural highlights
FunctionBT3A1_HUMAN Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.[1] [2] [3] [4] Publication Abstract from PubMedGamma delta (gammadelta) T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex-independent tumoricidal potential. Activation of gammadelta 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 alphabeta and gammadelta T cell responses remains unknown. Here, we report that the butyrophilin BTN3A1 inhibits tumor-reactive alphabeta T cell receptor activation by preventing segregation of N-glycosylated CD45 from the immune synapse. Notably, CD277-specific antibodies elicit coordinated restoration of alphabeta T cell effector activity and BTN2A1-dependent gammadelta lymphocyte cytotoxicity against BTN3A1(+) cancer cells, abrogating malignant progression. Targeting BTN3A1 therefore orchestrates cooperative killing of established tumors by alphabeta and gammadelta T cells and may present a treatment strategy for tumors resistant to existing immunotherapies. BTN3A1 governs antitumor responses by coordinating alphabeta and gammadelta T cells.,Payne KK, Mine JA, Biswas S, Chaurio RA, Perales-Puchalt A, Anadon CM, Costich TL, Harro CM, Walrath J, Ming Q, Tcyganov E, Buras AL, Rigolizzo KE, Mandal G, Lajoie J, Ophir M, Tchou J, Marchion D, Luca VC, Bobrowicz P, McLaughlin B, Eskiocak U, Schmidt M, Cubillos-Ruiz JR, Rodriguez PC, Gabrilovich DI, Conejo-Garcia JR Science. 2020 Aug 21;369(6506):942-949. doi: 10.1126/science.aay2767. PMID:32820120[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Anadon CM | Biswas S | Bobrowicz P | Buras AL | Chaurio RA | Conejo-Garcia JR | Costich TL | Cubillos-Ruiz JR | Eskiocak U | Gabrilovich DI | Harro CM | Lajoie J | Luca VC | Mandal G | Marchion D | McLaughlin B | Mine JA | Ming Q | Ophir M | Payne KK | Perales-Puchalt A | Rigolizzo KE | Rodriguez PC | Schmidt M | Tchou J | Tcyganov E | Walrath J
