title: Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E.
abstract: Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ(+) T cells, at ~4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8(+) T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Scott 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, OR 97006, USA.
authors.forename: Helen 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, OR 97006, USA.
authors.forename: Benjamin 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, OR 97006, USA.
authors.forename: Colette M
authors.initials: CM
authors.lastname: Hughes
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Katherine 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, OR 97006, USA.
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Ventura
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Jason 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, OR 97006, USA.
authors.forename: Roxanne M
authors.initials: RM
authors.lastname: Gilbride
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Ainslie
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: David 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, OR 97006, USA.
authors.forename: Julia 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, OR 97006, USA.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Selseth
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Reesab
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Malouli
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Michael 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, OR 97006, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Gillespie
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK.
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Walters
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Brackenridge
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Sharpe
authors.affiliation: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: César A
authors.initials: CA
authors.lastname: López
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Früh
authors.affiliation: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. The New Mexico Consortium, Los Alamos, NM 87545, USA.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gnanakaran
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000940:Antigenic Variation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000276:immunology; D008253:Macaca mulatta; D017433:Protein Structure, Secondary; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I