Abstract
Natural killer T cells express a conserved, semi-invariant alphabeta T cell receptor that has specificity for self glycosphingolipids and microbial cell wall alpha-glycuronosylceramide antigens presented by CD1d molecules. Here we report the crystal structure of CD1d in complex with a short-chain synthetic variant of alpha-galactosylceramide at a resolution of 2.2 A. This structure elucidates the basis for the high specificity of these microbial ligands and explains the restriction of the alpha-linkage as a unique pathogen-specific pattern-recognition motif. Comparison of the binding of altered lipid ligands to CD1d and T cell receptors suggested that the differential T helper type 1-like and T helper type 2-like properties of natural killer T cells may originate largely from differences in their 'loading' in different cell types and hence in their tissue distribution in vivo.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Animals
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Antigens, CD1 / biosynthesis
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Antigens, CD1d
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Cell Wall / metabolism
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Flow Cytometry
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Galactosylceramides / chemistry
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Glycosphingolipids / chemistry
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Hot Temperature
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Humans
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Isoelectric Focusing
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Killer Cells, Natural / chemistry
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Killer Cells, Natural / immunology*
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Ligands
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Lipids / chemistry
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Lymphocyte Activation
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Mice
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Models, Chemical
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Models, Molecular
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Mutation
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Protein Conformation
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell, alpha-beta / chemistry*
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Receptors, Antigen, T-Cell, alpha-beta / physiology*
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Recombinant Proteins / chemistry
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Structure-Activity Relationship
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Surface Plasmon Resonance
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Temperature
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Th1 Cells / metabolism
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Th2 Cells / metabolism
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Time Factors
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Tissue Distribution
Substances
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Antigens, CD1
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Antigens, CD1d
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CD1D protein, human
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Galactosylceramides
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Glycosphingolipids
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Ligands
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Lipids
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Recombinant Proteins
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alpha-galactosylceramide