title: Human mucosal associated invariant T cells detect bacterially infected cells.
abstract: Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtb-uninfected individuals. Interestingly, these Mtb-reactive cells expressed the Valpha7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, United States of America. goldm@ohsu.edu
authors.forename: Marielle C
authors.initials: MC
authors.lastname: Gold
authors.forename: Stefania
authors.initials: S
authors.lastname: Cerri
authors.forename: Susan
authors.initials: S
authors.lastname: Smyk-Pearson
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Cansler
authors.forename: Todd M
authors.initials: TM
authors.lastname: Vogt
authors.forename: Jacob
authors.initials: J
authors.lastname: Delepine
authors.forename: Ervina
authors.initials: E
authors.lastname: Winata
authors.forename: Gwendolyn M
authors.initials: GM
authors.lastname: Swarbrick
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chua
authors.forename: Yik Y L
authors.initials: YY
authors.lastname: Yu
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Cook
authors.forename: Megan D
authors.initials: MD
authors.lastname: Null
authors.forename: David B
authors.initials: DB
authors.lastname: Jacoby
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Harriff
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
mesh_terms: D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D022801:Complementarity Determining Regions; D003429:Cross Reactions; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology
chemical_list: D022801:Complementarity Determining Regions; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell