title: Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor.
abstract: Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ T cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present the crystal structure of a human Vα7.2Jα33-Vβ2 MAIT TCR. Mutagenesis revealed highly conserved requirements for the MAIT TCR-MR1 interaction across different human MAIT TCRs stimulated by distinct microbial sources. Individual residues within the MAIT TCR β chain were dispensable for the interaction with MR1, whereas the invariant MAIT TCR α chain controlled specificity through a small number of residues, which are conserved across species and located within the Vα-Jα regions. Mutagenesis of MR1 showed that only two residues, which were centrally positioned and on opposing sides of the antigen-binding cleft of MR1, were essential for MAIT cell activation. The mutagenesis data are consistent with a centrally located MAIT TCR-MR1 docking that was dominated by the α chain of the MAIT TCR. This candidate docking mode contrasts with that of the NKT TCR-CD1d-antigen interaction, in which both the α and β chain of the NKT TCR is required for ligation above the F'-pocket of CD1d.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Rangsima
authors.initials: R
authors.lastname: Reantragoon
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Illing
authors.forename: Mugdha
authors.initials: M
authors.lastname: Bhati
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kostenko
authors.forename: Mandvi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Meehan
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D055610:Antigens, CD1d / Q000502:physiology; D002460:Cell Line; D022801:Complementarity Determining Regions; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D055672:Static Electricity
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D022801:Complementarity Determining Regions; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell