5vcj

Structure of alpha-galactosylphytosphingosine bound by CD1d and in complex with the Va14Vb8.2 TCR

spinqualitylabelsall models 5vcj, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vcj is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.16Å Ligands: BMA, FUC, MAN, N57, NAG, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells. Publication Abstract from PubMed Activated NKT cells can stimulate antigen-presenting cells leading to enhanced peptide antigen-specific immunity. However, administration of potent NKT cell agonists like alpha-galactosylceramide (alpha-GalCer) can be associated with release of high levels of cytokines, and in some situations, hepatotoxicity. Here we show that it is possible to provoke sufficient NKT cell activity to stimulate strong antigen-specific T cell responses without these unwanted effects. This was achieved by chemically conjugating antigenic peptides to alpha-galactosylphytosphingosine (alpha-GalPhs), an NKT cell agonist with very weak activity based on structural characterisation and biological assays. Conjugation improved delivery to antigen-presenting cells in vivo, while use of a cathepsin-sensitive linker to release the alpha-GalPhs and peptide within the same cell promoted strong T cell activation and therapeutic anti-tumour responses in mice. The conjugates activated human NKT cells and enhanced human T cell responses to a viral peptide in vitro. Accordingly, we have demonstrated a means to safely exploit the immunostimulatory properties of NKT cells to enhance T cell activation for virus- and tumour-specific immunity. Enhancing T cell responses and tumour immunity by vaccination with peptides conjugated to a weak NKT cell agonist.,Compton BJ, Farrand KJ, Tang CW, Osmond TL, Speir M, Authier-Hall A, Wang J, Ferguson PM, Chan STS, Anderson RJ, Cooney TR, Hayman CM, Williams GM, Brimble MA, Brooks CR, Yong LK, Metelitsa LS, Zajonc DM, Godfrey DI, Gasser O, Weinkove R, Painter GF, Hermans IF Org Biomol Chem. 2019 Jan 31;17(5):1225-1237. doi: 10.1039/c8ob02982b. PMID:30656346 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures CD1

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