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Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy.
Verweij, Marieke C; Hansen, Scott G; Iyer, Ravi; John, Nessy; Malouli, Daniel; Morrow, David; Scholz, Isabel; Womack, Jennie; Abdulhaqq, Shaheed; Gilbride, Roxanne M; Hughes, Colette M; Ventura, Abigail B; Ford, Julia C; Selseth, Andrea N; Oswald, Kelli; Shoemaker, Rebecca; Berkemeier, Brian; Bosche, William J; Hull, Michael; Shao, Jason; Sacha, Jonah B; Axthelm, Michael K; Edlefsen, Paul T; Lifson, Jeffrey D; Picker, Louis J; Früh, Klaus.
Afiliación
  • Verweij MC; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Hansen SG; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Iyer R; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • John N; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Malouli D; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Morrow D; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Scholz I; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Womack J; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Abdulhaqq S; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Gilbride RM; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Hughes CM; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Ventura AB; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Ford JC; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Selseth AN; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Oswald K; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Shoemaker R; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Berkemeier B; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Bosche WJ; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Hull M; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Shao J; Population Sciences and Computational Biology Programs, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Sacha JB; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Axthelm MK; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
  • Edlefsen PT; Population Sciences and Computational Biology Programs, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Lifson JD; AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.
  • Picker LJ; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA. fruehk@ohsu.edu pickerl@ohsu.edu.
  • Früh K; Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA. fruehk@ohsu.edu pickerl@ohsu.edu.
Science ; 372(6541)2021 04 30.
Article en En | MEDLINE | ID: mdl-33766941
ABSTRACT
Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+ T cells recognizing epitopes presented by major histocompatibility complex II (MHC-II) and MHC-E but not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular MHC-E transport and recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8+ T cells. Deletion or mutation of viral VL9 abrogated MHC-E-restricted CD8+ T cell priming, resulting in CD8+ T cell responses exclusively targeting MHC-II-restricted epitopes. These responses were comparable in magnitude and differentiation to responses elicited by 68-1 vectors but did not protect against SIV. Thus, Rh67-enabled direct priming of MHC-E-restricted T cells is crucial for RhCMV/SIV vaccine efficacy.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Antígenos de Histocompatibilidad Clase I / Vacunas contra el SIDAS / Linfocitos T CD8-positivos / Citomegalovirus / Vectores Genéticos Límite: Animals Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Antígenos de Histocompatibilidad Clase I / Vacunas contra el SIDAS / Linfocitos T CD8-positivos / Citomegalovirus / Vectores Genéticos Límite: Animals Idioma: En Revista: Science Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos