Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV
Author(s)
Type
Journal Article
Abstract
Human herpesviruses are important causes of potentially severe chronic infections for which T cells are believed to be necessary for control. In order to examine the role of virus-specific CD8 T cells against Varicella Zoster Virus (VZV), we generated a comprehensive panel of potential epitopes predicted in silico and screened for T cell responses in healthy VZV seropositive donors. We identified a dominant HLA-A*0201-restricted epitope in the VZV ribonucleotide reductase subunit 2 and used a tetramer to analyze the phenotype and function of epitope-specific CD8 T cells. Interestingly, CD8 T cells responding to this VZV epitope also recognized homologous epitopes, not only in the other α-herpesviruses, HSV-1 and HSV-2, but also the γ-herpesvirus, EBV. Responses against these epitopes did not depend on previous infection with the originating virus, thus indicating the cross-reactive nature of this T cell population. Between individuals, the cells demonstrated marked phenotypic heterogeneity. This was associated with differences in functional capacity related to increased inhibitory receptor expression (including PD-1) along with decreased expression of co-stimulatory molecules that potentially reflected their stimulation history. Vaccination with the live attenuated Zostavax vaccine did not efficiently stimulate a proliferative response in this epitope-specific population. Thus, we identified a human CD8 T cell epitope that is conserved in four clinically important herpesviruses but that was poorly boosted by the current adult VZV vaccine. We discuss the concept of a “pan-herpesvirus” vaccine that this discovery raises and the hurdles that may need to be overcome in order to achieve this.
Date Issued
2014-03-01
Online Publication Date
2020-09-10T10:07:40Z
Date Acceptance
2014-02-03
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
12
Journal / Book Title
PLoS Pathogens
Volume
10
Issue
3
Copyright Statement
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Identifier
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004008
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337470300050&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
G0902266
G1000758
G1000758
NF-SI-0513-10150
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
VARICELLA-ZOSTER-VIRUS
EPSTEIN-BARR-VIRUS
IMMUNE EVASION
HERPES-ZOSTER
RESPONSES
INFECTION
ANTIGENS
DELETION
VACCINE
Adult
CD8-Positive T-Lymphocytes
Cross Reactions
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte
Flow Cytometry
HLA-A2 Antigen
Herpes Zoster Vaccine
Herpesvirus 3, Human
Herpesvirus 4, Human
Humans
Simplexvirus
Viral Vaccines
CD8-Positive T-Lymphocytes
Humans
Simplexvirus
Herpesvirus 3, Human
Herpesvirus 4, Human
Viral Vaccines
HLA-A2 Antigen
Epitopes, T-Lymphocyte
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Cross Reactions
Adult
Herpes Zoster Vaccine
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
VARICELLA-ZOSTER-VIRUS
EPSTEIN-BARR-VIRUS
IMMUNE EVASION
HERPES-ZOSTER
RESPONSES
INFECTION
ANTIGENS
DELETION
VACCINE
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Virology
Publication Status
Published
Article Number
ARTN e1004008
Date Publish Online
2014-03-27