Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V(alpha)14 NKT cells.
A novel lymphocyte, NKT cells bearing an invariant V(alpha)14 antigen receptor, specifically recognizes alpha-galactosylceramide (alpha-GalCer) exclusively presented by mouse CD1d (mCD1d). However, the precise molecular interaction remains unclear. For the basis of functional analyses, a docking model of alpha-GalCer with the crystal structure of mCD1d was constructed. Possible residues involved in the alpha-GalCer--mCD1d interaction were found to be Arg79, Glu83 and Asp80 for carbohydrate recognition, and Asp153 for interaction with the amide group on the fatty acyl chain. The alpha-GalCer-presenting ability of various transfectants expressing mutant mCD1d was completely abrogated if a single amino acid mutation was induced at positions 79, 80, 83 or 153, suggesting that the polar amino acids above the F' pocket are crucial for alpha-GalCer presentation to activate V(alpha)14 NKT cells. The possibility that Glu83 is a contact site for the NKT cell receptor is also discussed.
Kamada
N
N
Core Research for Evolutional Science and Technology and Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Iijima
H
H
Kimura
K
K
Harada
M
M
Shimizu
E
E
Motohashi Si
Kawano
T
T
Shinkai
H
H
Nakayama
T
T
Sakai
T
T
Brossay
L
L
Kronenberg
M
M
Taniguchi
M
M
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d; D001665:Binding Sites; D003198:Computer Simulation; D005260:Female; D005963:Glucosylceramides / Q000737:chemistry* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000596:Amino Acids; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005963:Glucosylceramides; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta