6MJQ

Crystal structure of the mCD1d/xxp (JJ295) /iNKTCR ternary complex

Summary for 6MJQ

• Entry DOI: 10.2210/pdb6mjq/pdb
• Descriptor: T cell receptor alpha variable 11,T cell receptor alpha variable 11,T cell receptor alpha joining 18,Human nkt tcr alpha chain, chimeric protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-{(2S,3S,4R)-3,4-dihydroxy-1-[(4-O-{[4-(trifluoromethyl)phenyl]methyl}-alpha-D-galactopyranosyl)oxy]octadecan-2-yl}hexacosanamide, ... (12 entities in total)
• Functional Keywords: mhc-fold, ig-fold, glycolipid antigen presentation, t cell receptor, immune system, immune system-inhibitor complex, immune system/inhibitor
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 8
• Total formula weight: 194251.33

Authors

Zajonc, D.M.,Bitra, A.,Janssens, J. (deposition date: 2018-09-21, release date: 2019-01-09, Last modification date: 2024-11-20)

Primary citation

Janssens, J.,Bitra, A.,Wang, J.,Decruy, T.,Venken, K.,van der Eycken, J.,Elewaut, D.,Zajonc, D.M.,van Calenbergh, S.
4"-O-Alkylated alpha-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic, Biological, and Structural Studies.
ChemMedChem, 14:147-168, 2019

PubMed Abstract: Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, α-galactosylceramide (α-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of α-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4"-O-alkylated α-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4"-OH group to ether moieties decreases the immunogenic potential in mice relative to α-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the α2-helix of CD1d.

PubMed: 30556652
DOI: 10.1002/cmdc.201800649

Experimental method

X-RAY DIFFRACTION (3 Å)