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PMID: 16520393 Published · ppublish English Journal Article

Structure and binding kinetics of three different human CD1d-alpha-galactosylceramide-specific T cell receptors.

The Journal of experimental medicine ·Vol. 203 ·No. 3 ·2006-03-20 ·Pages 699-710

Gadola SD, Koch M, Marles-Wright J, Lissin NM, Shepherd D, Matulis G, Harlos K, Villiger PM, Stuart DI, Jakobsen BK, Cerundolo V, Jones EY

Abstract

Invariant human TCR Valpha24-Jalpha18+/Vbeta11+ NKT cells (iNKT) are restricted by CD1d-alpha-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d-alpha-GalCer-specific Vbeta11+ TCRs that use different TCR Valpha chains. The results were similar to those previously reported for MHC-peptide-specific TCRs, illustrating the versatility of the TCR platform. Docking TCR and CD1d-alpha-GalCer structures provided plausible insights into their interaction. The model supports a diagonal orientation of TCR on CD1d and suggests that complementarity determining region (CDR)3alpha, CDR3beta, and CDR1beta interact with ligands presented by CD1d, whereas CDR2beta binds to the CD1d alpha1 helix. This docking provides an explanation for the dominant usage of Vbeta11 and Vbeta8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-alpha-GalCer.

MeSH Terms
Animals Antigen Presentation/immunology Antigens, CD1/chemistry,immunology Antigens, CD1d Complementarity Determining Regions/chemistry,immunology Crystallography, X-Ray Galactosylceramides/chemistry,immunology Humans Killer Cells, Natural/immunology Mice Models, Molecular Protein Binding/immunology Protein Structure, Quaternary Receptors, Antigen, T-Cell, alpha-beta/chemistry,immunology Structure-Activity Relationship T-Lymphocytes/immunology
Chemicals
Antigens, CD1 Antigens, CD1d CD1D protein, human Complementarity Determining Regions Galactosylceramides Receptors, Antigen, T-Cell, alpha-beta
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Gadola Stephan D
Department of Rheumathology and Clinical Immunology, University of Bern, Inselspital, Berne CH-3010, Switzerland. stephan.gadola@insel.ch
Koch Michael
Marles-Wright Jon
Lissin Nikolai M
Shepherd Dawn
Matulis Gediminas
Harlos Karl
Villiger Peter M
Stuart David I
Jakobsen Bent K
Cerundolo Vincenzo
Jones E Yvonne
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20052369
Email
stephan.gadola@insel.ch
Published
2006-03-20
Epub
2006-00-06
Pages
699-710
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118257
Subset
IM
Grants
Medical Research Council · G0500365 · United Kingdom
Medical Research Council · G0501975 · United Kingdom
Medical Research Council · G9900061 · United Kingdom
Databases
PDB
2CDE, 2CDF, 2CDG
External Links
PubMed source DOI: 10.1084/jem.20052369 PMC Full Text View journal details
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