title: Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms.
abstract: CD8(+) T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8(+) T cell epitope recognition.
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.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Colette M
authors.initials: CM
authors.lastname: Hughes
authors.forename: Julia C
authors.initials: JC
authors.lastname: Ford
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Isabel
authors.initials: I
authors.lastname: Scholz
authors.forename: Roxanne M
authors.initials: RM
authors.lastname: Gilbride
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lewis
authors.forename: Awbrey N
authors.initials: AN
authors.lastname: Gilliam
authors.forename: Abigail B
authors.initials: AB
authors.lastname: Ventura
authors.forename: Daniel
authors.initials: D
authors.lastname: Malouli
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richards
authors.forename: Nathan
authors.initials: N
authors.lastname: Whizin
authors.forename: Jason S
authors.initials: JS
authors.lastname: Reed
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Hammond
authors.forename: Miranda
authors.initials: M
authors.lastname: Fischer
authors.forename: John M
authors.initials: JM
authors.lastname: Turner
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Klaus
authors.initials: K
authors.lastname: Früh
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; C532797:UL128 protein, human cytomegalovirus; C502890:UL130 protein, human cytomegalovirus; D014759:Viral Envelope Proteins