title: Germline-encoded recognition of diverse glycolipids by natural killer T cells.
abstract: Natural killer T cells expressing 'invariant' T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J) region V(alpha)14-J(alpha)18 (V(alpha)14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRalpha chain and a restricted set of TCRbeta chains recognize structurally diverse antigens is not clear. Here we show that a V(alpha)14i TCR recognized many alpha-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3alpha, 1alpha and 2beta. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the V(alpha)14i TCR functions as a pattern-recognition receptor, conferring on natural killer T cells the ability to sense and respond in an innate way to pathogens displaying antigenic alpha-linked glycolipids.
authors.affiliation: Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Scott-Browne
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Matsuda
authors.forename: Thierry
authors.initials: T
authors.lastname: Mallevaey
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Borg
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: John
authors.initials: J
authors.lastname: Kappler
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology; D055610:Antigens, CD1d; D022801:Complementarity Determining Regions; D003461:Crystallography; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000502:physiology*