title: CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor.
abstract: The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d-antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist alpha-galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor-peptide-antigen-MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR alpha-chain and the CD1d-antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR beta-chain can impact on recognition of other CD1d-antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.
authors.affiliation: The Protein Crystallography Unit, ARC 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: Natalie A
authors.initials: NA
authors.lastname: Borg
authors.forename: Kwok S
authors.initials: KS
authors.lastname: Wun
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Matthew C J
authors.initials: MC
authors.lastname: Wilce
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Ruide
authors.initials: R
authors.lastname: Koh
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Mandvi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology*; D055610:Antigens, CD1d; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide