| Literature DB >> 33766941 |
Marieke C Verweij1, Scott G Hansen1, Ravi Iyer1, Nessy John1, Daniel Malouli1, David Morrow1, Isabel Scholz1, Jennie Womack1, Shaheed Abdulhaqq1, Roxanne M Gilbride1, Colette M Hughes1, Abigail B Ventura1, Julia C Ford1, Andrea N Selseth1, Kelli Oswald2, Rebecca Shoemaker2, Brian Berkemeier2, William J Bosche2, Michael Hull2, Jason Shao3, Jonah B Sacha1, Michael K Axthelm1, Paul T Edlefsen3, Jeffrey D Lifson2, Louis J Picker4, Klaus Früh4.
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.Entities:
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Year: 2021 PMID： 33766941 DOI： 10.1126/science.abe9233
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728