title: Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
abstract: The semi-invariant natural killer (NK) T-cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the alpha-chain of the NKTcr is invariant, the beta-chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an alpha-linked monosaccharide (alpha-galactosylceramide and alpha-galactosyldiacylglycerol) and the beta-linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their beta-chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including alpha-galactosylceramide, the structurally similar alpha-galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr beta-chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr beta-chain allows these cells to recognise unique aspects of structurally diverse CD1d-restricted ligands.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Florence
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Xia
authors.forename: Laura E
authors.initials: LE
authors.lastname: Gordy
authors.forename: Wenlan
authors.initials: W
authors.lastname: Chen
authors.forename: Yalong
authors.initials: Y
authors.lastname: Zhang
authors.forename: James
authors.initials: J
authors.lastname: Scott-Browne
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Karl O A
authors.initials: KO
authors.lastname: Yu
authors.forename: Santosh
authors.initials: S
authors.lastname: Keshipeddy
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Stewart K
authors.initials: SK
authors.lastname: Richardson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Amy R
authors.initials: AR
authors.lastname: Howell
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Zajonc
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
mesh_terms: D000220:Adaptation, Biological / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D055611:Natural Killer T-Cells / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D015295:Antigens, Tumor-Associated, Carbohydrate; D005699:Galactosylceramides; C472766:Gb3 antigen; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide