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Published online 6 March 2006 doi:10.1084/jem.20052369
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 699-710
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ARTICLE

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

Stephan D. Gadola1,2, Michael Koch3, Jon Marles-Wright3, Nikolai M. Lissin4, Dawn Shepherd2, Gediminas Matulis1, Karl Harlos3, Peter M. Villiger1, David I. Stuart3, Bent K. Jakobsen4, Vincenzo Cerundolo2, and E. Yvonne Jones3

1 Department of Rheumathology and Clinical Immunology, University of Bern, Inselspital, Berne CH-3010, Switzerland
2 Cancer Research UK Tumor Immunology Group, The Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, UK
3 Cancer Research UK Receptor Structure Research Group, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK
4 Avidex, OX14 4RX Abingdon, UK

CORRESPONDENCE E.Y. Jones: yvonne{at}strubi.ox.ac.uk OR S.D. Gadola: stephan.gadola{at}insel.ch

Invariant human TCR V{alpha}24-J{alpha}18+/Vß11+ 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 Vß11+ TCRs that use different TCR V{alpha} 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)3{alpha}, CDR3ß, and CDR1ß interact with ligands presented by CD1d, whereas CDR2ß binds to the CD1d {alpha}1 helix. This docking provides an explanation for the dominant usage of Vß11 and Vß8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d–{alpha}-GalCer.


Abbreviations used: {alpha}-GalCer, {alpha}-galactosylceramide; CDR, complementarity determining region; CNS, Crystallography and NMR system; DN, double negative; ds, disulfide-linked; iNKT, invariant NKT; J, junctional; PC, phosphatidylcholine; rmsd, root mean square deviation; V, variable.

V. Cerundolo and E.Y. Jones share senior authorship.

S.D. Gadola, M. Koch, and J. Marles-Wright contributed equally to this work.


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