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

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 response

SUBMITTER: Verweij MC 

PROVIDER: S-EPMC8354429 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature