title: A semi-invariant Vα10+ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties.
abstract: Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(α)14-J(α)18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α-GalCer-reactive NKT cells that expressed a canonical V(α)10-J(α)50 TCR α-chain, which showed a preference for α-glucosylceramide (α-GlcCer) and bacterial α-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRα sequence identity, the V(α)10 TCR-CD1d-α-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-α-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
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: E Bridie
authors.initials: EB
authors.lastname: Day
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kyparissoudis
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Julian P
authors.initials: JP
authors.lastname: Vivian
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cao
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Williams
authors.forename: Petr
authors.initials: P
authors.lastname: Illarionov
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D002460:Cell Line; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D005965:Glucuronates / Q000276:immunology; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D055610:Antigens, CD1d; D005699:Galactosylceramides; D005965:Glucuronates; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide; C103873:KRN 7000