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

Gadola, Stephan D., 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 and Jones, E. Yvonne (2006) Structure and binding kinetics of three different human CD1d-?-galactosylceramide-specific T cell receptors. The Journal of Experimental Medicine, 203 (3), 699-710. (doi:10.1084/jem.20052369).

Abstract

Invariant human TCR V?24-J?18+/Vbeta11+ NKT cells (iNKT) are restricted by CD1d-?-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d-?-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-?-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?, CDR3?, and CDR1? interact with ligands presented by CD1d, whereas CDR2? binds to the CD1d ?1 helix. This docking provides an explanation for the dominant usage of V?11 and V?8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d-?-GalCer.

Abbreviations used: ?-GalCer, ?-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.

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