4f9p
Crystal Structure of the Human BTN3A1 Ectodomain in Complex with the 103.2 Single Chain Antibody
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 PubMedHuman Vgamma9Vdelta2 T cells are well known for their rapid and potent response to infection and tumorigenesis when in the presence of endogenous or exogenous phosphoisoprenoids. However, the molecular mechanisms behind the activation of this gammadelta T cell population remains unclear. Evidence pointing to a role for the CD277/butyrophilin-3 (BTN3A) molecules in this response led us to investigate the structures of these molecules and their modifications upon binding to an agonist antibody (20.1) that mimics phosphoisoprenoid-mediated Vgamma9Vdelta2 activation and an antagonist antibody (103.2) that inhibits this reactivity. We find that the three BTN3A isoforms: BTN3A1, BTN3A2, and BTN3A3, have high structural homology to the B7 superfamily of proteins and exist as V-shaped homodimers in solution, associating through the membrane proximal C-type Ig domain. The 20.1 and 103.2 antibodies bind to separate epitopes on the BTN3A Ig-V domain with high affinity but likely with different valencies based on their binding orientation. These structures directly complement functional studies of this system that demonstrate that BTN3A1 is necessary for Vgamma9Vdelta2 activation and begin to unravel the extracellular events that occur during stimulation through the Vgamma9Vdelta2 T cell receptor. The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by CD277/butyrophilin-3 (BTN3A)-specific antibodies.,Palakodeti A, Sandstrom A, Sundaresan L, Harly C, Nedellec S, Olive D, Scotet E, Bonneville M, Adams EJ J Biol Chem. 2012 Sep 21;287(39):32780-90. Epub 2012 Jul 30. PMID:22846996[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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