Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.
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.
Zajonc
Dirk M
DM
Department of Molecular Biology and The Scripps Research Institute, La Jolla, California 92037, USA.
Cantu
Carlos
C
Mattner
Jochen
J
Zhou
Dapeng
D
Savage
Paul B
PB
Bendelac
Albert
A
Wilson
Ian A
IA
Teyton
Luc
L
D020816:Amino Acid Motifs; D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis; D055610:Antigens, CD1d; D002473:Cell Wall / Q000378:metabolism; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000737:chemistry; D006028:Glycosphingolipids / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D007525:Isoelectric Focusing; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008213:Lymphocyte Activation; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D013696:Temperature; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D006028:Glycosphingolipids; D008024:Ligands; D008055:Lipids; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C493154:alpha-galactosylceramide