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PMID: 16007091 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor.

Nature immunology ·Vol. 6 ·No. 8 ·2005-08-00 ·Pages 810-8

Zajonc DM, Cantu C, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L

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.

MeSH Terms
Amino Acid Motifs Animals Antigens, CD1/biosynthesis Antigens, CD1d Cell Wall/metabolism Crystallography, X-Ray Dose-Response Relationship, Drug Flow Cytometry Galactosylceramides/chemistry Glycosphingolipids/chemistry Hot Temperature Humans Isoelectric Focusing Killer Cells, Natural/chemistry,immunology Ligands Lipids/chemistry Lymphocyte Activation Mice Models, Chemical Models, Molecular Mutation Protein Conformation Receptors, Antigen, T-Cell/chemistry,immunology Receptors, Antigen, T-Cell, alpha-beta/chemistry,physiology Recombinant Proteins/chemistry Structure-Activity Relationship Surface Plasmon Resonance Temperature Th1 Cells/metabolism Th2 Cells/metabolism Time Factors Tissue Distribution
Chemicals
Antigens, CD1 Antigens, CD1d CD1D protein, human Galactosylceramides Glycosphingolipids Ligands Lipids Receptors, Antigen, T-Cell Receptors, Antigen, T-Cell, alpha-beta Recombinant Proteins alpha-galactosylceramide
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zajonc Dirk M
Department of Molecular Biology and The Scripps Research Institute, La Jolla, California 92037, USA.
Cantu Carlos
Mattner Jochen
Zhou Dapeng
Savage Paul B
Bendelac Albert
Wilson Ian A
Teyton Luc
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2908
DOI
10.1038/ni1224
Published
2005-08-00
Epub
2005-00-10
Pages
810-8
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2045075
Subset
IM
Grants
NIAID NIH HHS · AI053725 · United States
NCI NIH HHS · R01 CA058896 · United States
NIAID NIH HHS · P01 AI053725 · United States
NCI NIH HHS · CA58896 · United States
NIAID NIH HHS · P01 AI053725-010002 · United States
NIGMS NIH HHS · GM62116 · United States
NIGMS NIH HHS · U54 GM062116 · United States
Corrections
CommentIn
PMID: 16034430
External Links
PubMed source DOI: 10.1038/ni1224 PMC Full Text View journal details
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