Modulation of MHC-E Transport by Viral Decoy Ligands is Required for RhCMV/SIV Vaccine Efficacy

Overview

Journal Science

Specialty Science

Date 2021 Mar 26

PMID 33766941

Citations 31

Authors

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 Shao

Jonah B Sacha

Michael K Axthelm

Paul T Edlefsen

Jeffrey D Lifson

Louis J Picker

Klaus Fruh

Affiliations

Soon will be listed here.

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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