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

Marieke C. Verweij, Scott G. Hansen, Ravi Iyer, Nessy John, Daniel Malouli, David Morrow, Isabel Scholz, Jennie Womack, Shaheed Abdulhaqq, Roxanne M. Gilbride, Colette M. Hughes, Abigail B. Ventura, Julia C. Ford, Andrea N. Selseth, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Jason ShaoJonah B. Sacha, Michael K. Axthelm, Paul T. Edlefsen, Jeffrey D. Lifson, Louis J. Picker, Klaus Früh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbereabe9233
JournalScience
Volume372
Issue number6541
DOIs
StatePublished - Apr 30 2021

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy'. Together they form a unique fingerprint.

Cite this