Cytomegalovirus Vectors Violate CD8+ T Cell Epitope Recognition Paradigms

Overview

Journal Science

Specialty Science

Date 2013 May 25

PMID 23704576

Citations 284

Authors

Scott G Hansen

Jonah B Sacha

Colette M Hughes

Julia C Ford

Benjamin J Burwitz

Isabel Scholz

Roxanne M Gilbride

Matthew S Lewis

Awbrey N Gilliam

Abigail B Ventura

Daniel Malouli

Guangwu Xu

Rebecca Richards

Nathan Whizin

Jason S Reed

Katherine B Hammond

Miranda Fischer

John M Turner

Alfred W Legasse

Michael K Axthelm

Paul T Edlefsen

Jay A Nelson

Jeffrey D Lifson

Klaus Fruh

Louis J Picker

Affiliations

Soon will be listed here.

Abstract

CD8(+) T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8(+) T cell epitope recognition.

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