title: Recognition of vitamin B metabolites by mucosal-associated invariant T cells.
abstract: The mucosal-associated invariant T-cell antigen receptor (MAIT TCR) recognizes MR1 presenting vitamin B metabolites. Here we describe the structures of a human MAIT TCR in complex with human MR1 presenting a non-stimulatory ligand derived from folic acid and an agonist ligand derived from a riboflavin metabolite. For both vitamin B antigens, the MAIT TCR docks in a conserved manner above MR1, thus acting as an innate-like pattern recognition receptor. The invariant MAIT TCR α-chain usage is attributable to MR1-mediated interactions that prise open the MR1 cleft to allow contact with the vitamin B metabolite. Although the non-stimulatory antigen does not contact the MAIT TCR, the stimulatory antigen does. This results in a higher affinity of the MAIT TCR for a stimulatory antigen in comparison with a non-stimulatory antigen. We formally demonstrate a structural basis for MAIT TCR recognition of vitamin B metabolites, while illuminating how TCRs recognize microbial metabolic signatures.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Nours
authors.forename: Sidonia B G
authors.initials: SB
authors.lastname: Eckle
authors.forename: Richard
authors.initials: R
authors.lastname: Birkinshaw
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Corbett
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Meehan
authors.forename: Rangsima
authors.initials: R
authors.lastname: Reantragoon
authors.forename: Maria L
authors.initials: ML
authors.lastname: Sandoval-Romero
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Chen
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D015778:Minor Histocompatibility Antigens; D062105:Molecular Docking Simulation; D054730:Protein Interaction Domains and Motifs; D058849:Protein Refolding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012256:Riboflavin / Q000737:chemistry* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D005492:Folic Acid; D012256:Riboflavin