title: NKT TCR recognition of CD1d-α-C-galactosylceramide.
abstract: NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are structurally related to the prototypic Ag α-galactosylceramide (α-GalCer). A modified analog of α-GalCer with a carbon-based glycosidic linkage (α-C-GalCer) has generated great interest because of its apparent ability to promote prolonged, Th1-biased immune responses. In this study, we report the activation of spleen NKT cells to α-C-GalCer, and related C-glycoside ligands, is weaker than that of α-GalCer. Furthermore, the Vβ8.2 and Vβ7 NKT TCR affinity for CD1d-α-C-GalCer, and some related analogs, is ∼10-fold lower than that for the NKT TCR-CD1d-α-GalCer interaction. Nevertheless, the crystal structure of the Vβ8.2 NKT TCR-CD1d-α-C-GalCer complex is similar to that of the corresponding NKT TCR-CD1d-α-GalCer complex, although subtle differences at the interface provide a basis for understanding the lower affinity of the NKT TCR-CD1d-α-C-GalCer interaction. Our findings support the concept that for CD1d-restricted NKT cells, altered glycolipid ligands can promote markedly different responses while adopting similar TCR-docking topologies.
authors.affiliation: Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Garth
authors.initials: G
authors.lastname: Cameron
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Hoe-Sup
authors.initials: HS
authors.lastname: Byun
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Richard W
authors.initials: RW
authors.lastname: Franck
authors.forename: A Raúl
authors.initials: AR
authors.lastname: Castaño
authors.forename: Youssef
authors.initials: Y
authors.lastname: Harrak
authors.forename: Amadeu
authors.initials: A
authors.lastname: Llebaria
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D005699:Galactosylceramides / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D005699:Galactosylceramides; D008024:Ligands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2