title: Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors.
abstract: The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid antigens. Although the TCR alpha chain is typically invariant, the beta chain expression is more diverse, where three V beta chains are commonly expressed in mice. We report the structures of V alpha 14-V beta 8.2 and V alpha 14-V beta 7 NKT TCRs in complex with CD1d-alpha-galactosylceramide (alpha-GalCer) and the 2.5 A structure of the human NKT TCR-CD1d-alpha-GalCer complex. Both V beta 8.2 and V beta 7 NKT TCRs and the human NKT TCR ligated CD1d-alpha-GalCer in a similar manner, highlighting the evolutionarily conserved interaction. However, differences within the V beta domains of the V beta 8.2 and V beta 7 NKT TCR-CD1d complexes resulted in altered TCR beta-CD1d-mediated contacts and modulated recognition mediated by the invariant alpha chain. Mutagenesis studies revealed the differing contributions of V beta 8.2 and V beta 7 residues within the CDR2 beta loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V beta usage in NKT cells.
authors: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors: Daniel G
authors: DG
authors: Pellicci
authors: Onisha
authors: O
authors: Patel
authors: Lars
authors: L
authors: Kjer-Nielsen
authors: Siew Siew
authors: SS
authors: Pang
authors: Lucy C
authors: LC
authors: Sullivan
authors: Konstantinos
authors: K
authors: Kyparissoudis
authors: Andrew G
authors: AG
authors: Brooks
authors: Hugh H
authors: HH
authors: Reid
authors: Stephanie
authors: S
authors: Gras
authors: Isabelle S
authors: IS
authors: Lucet
authors: Ruide
authors: R
authors: Koh
authors: Mark J
authors: MJ
authors: Smyth
authors: Thierry
authors: T
authors: Mallevaey
authors: Jennifer L
authors: JL
authors: Matsuda
authors: Laurent
authors: L
authors: Gapin
authors: James
authors: J
authors: McCluskey
authors: Dale I
authors: DI
authors: Godfrey
authors: Jamie
authors: J
authors: Rossjohn
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000737:chemistry / Q000276:immunology*; D003001:Cloning, Molecular; D003460:Crystallization; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D055611:Natural Killer T-Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; C493154:alpha-galactosylceramide