title: MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates.
abstract: Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts. Using the macaque MR1 tetramer we show that NHP MAITs activated in vivo in response to both Bacillus Calmette-Guerin vaccination and Mycobacterium tuberculosis infection. These results demonstrate that NHP and human MR1 and MAITs function analogously, and establish a preclinical animal model to test MAIT-targeted vaccines and therapeutics for human infectious and autoimmune disease.
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Greene
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: P
authors.initials: P
authors.lastname: Dash
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: C
authors.initials: C
authors.lastname: McMurtrey
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: W
authors.initials: W
authors.lastname: Awad
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Reed
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Hammond
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abdulhaqq
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Wu
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Burwitz
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Roth
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Morrow
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Ford
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: H
authors.initials: H
authors.lastname: Crank
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Legasse
authors.affiliation: UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: T H
authors.initials: TH
authors.lastname: Dang
authors.affiliation: UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: H Y
authors.initials: HY
authors.lastname: Greenaway
authors.affiliation: UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Kurniawan
authors.affiliation: Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Gold
authors.affiliation: Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA.|VA Portland Health Care Services, Research & Development, Portland, Oregon, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Harriff
authors.affiliation: Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lewinsohn
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Park
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Axthelm
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Stanton
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Hansen
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Picker
authors.affiliation: Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Venturi
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hildebrand
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Lewinsohn
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.|Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Adams
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Sacha
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011485:Protein Binding; D015202:Protein Engineering; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; D032581:Tuberculosis Vaccines