Nature Immunology
3, 721 - 726 (2002)
Published online: 15 July 2002; | doi:10.1038/ni821
Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chainsStephan D. Gadola1, 5, 6, Nathan R. Zaccai2, 5, Karl Harlos2, Dawn Shepherd1, Julio C. Castro-Palomino3, Gerd Ritter4, Richard R. Schmidt3, E. Yvonne Jones2
& Vincenzo Cerundolo11
Cancer Research UK Tumour Immunology Group, The Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. 2
Cancer Research UK Receptor Structure Research Group, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK. 3
Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany. 4
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5
These authors contributed equally to this work. 6
Present address: Department of Rheumatology and Clinical Immunology, University of Berne, Inselspital, PKT2 D584, Berne CH-3010, Switzerland.
Correspondence should be addressed to Stephan D. Gadola stephan.gadola@insel.ch or E. Yvonne Jones yvonne@strubi.ox.ac.uk or Vincenzo Cerundolo vincenzo.cerundolo@imm.ox.ac.ukThe human genome encodes five nonpolymorphic major histocompatibility complex class I−like glycoproteins, CD1a to CD1e, that present lipid antigens for specific recognition by T lymphocytes. Using single alkyl chain detergents, we developed a protocol to generate recombinant human CD1b-lipid complexes. We present here the crystal structures of CD1b in complex with either phosphatidylinositol or ganglioside GM2 at 2.3 Å and 2.8 Å resolutions, respectively. The antigen-binding groove houses four interlinked hydrophobic channels that are occupied by the alkyl chains of the glycolipid plus two detergent molecules. A distinct exit beneath the  2 helix further contributes to the plasticity of the binding groove. These structures reveal the mechanism by which two alkyl chain lipids bind to CD1b, and how CD1b can adapt to ligands of different alkyl chain length. They also suggest how very long alkyl chains, such as those of mycolic acid, could be fully contained within the binding groove. These results extend the spectrum of potential CD1b ligands by revealing that, in addition to two alkyl chain lipids, mono-alkyl and triple-alkyl chain lipids can be accommodated in the binding groove.
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