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Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy.

Marieke C VerweijScott G HansenRavi F IyerNessy JohnDaniel MalouliDavid W MorrowIsabel ScholzJennie L WomackShaheed AbdulhaqqRoxanne M GilbrideColette M HughesAbigail B VenturaJulia C FordAndrea N SelsethKelli OswaldRebecca ShoemakerBrian BerkemeierWilliam J BoscheMichael HullDanica ShaoJonah B SachaMichael K AxthelmPaul T EdlefsenJeffrey D LifsonLouis J PickerKlaus Früh
Published in: Science (New York, N.Y.) (2021)
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.
Keyphrases
  • immune response
  • sars cov
  • cell proliferation
  • drug delivery
  • inflammatory response
  • cancer therapy
  • wild type