Epitopes described in "The context of gene expression defines the immunodominance hierarchy of cytomegalovirus antigens."

Article Authors:Iryna Dekhtiarenko; Michael A Jarvis; Zsolt Ruzsics; Luka Čičin-Šain
Article Title:The context of gene expression defines the immunodominance hierarchy of cytomegalovirus antigens.
Reference Detail
Reference ID:1025919
Abstract:Natural immunity to CMV dominates the CD4 and CD8 memory compartments of the CMV-seropositive host. This property has been recently exploited for experimental CMV-based vaccine vector strategies, and it has shown promise in animal models of AIDS and Ebola disease. Although it is generally agreed that CMV-based vaccine vectors may induce highly protective and persistent memory T cells, the influence of the gene expression context on Ag-specific T cell memory responses and immune protection induced by CMV vectors is not known. Using murine CMV (MCMV) recombinants expressing a single CD8 T cell epitope from HSV-1 fused to different MCMV genes, we show that magnitude and kinetics of T cell responses induced by CMV are dependent on the gene expression of CMV Ags. Interestingly, the kinetics of the immune response to the HSV-1 epitope was paralleled by a reciprocal depression of immune responses to endogenous MCMV Ags. Infection with a recombinant MCMV inducing a vigorous initial immune response to the recombinant peptide resulted in a depressed early response to endogenous MCMV Ag. Another recombinant virus, which induced a slowly developing "inflationary" T cell response to the HSV-1 peptide, induced weaker long-term responses to endogenous CMV Ags. Importantly, both mutants were able to protect mice from a challenge with HSV-1, mediating strong sterilizing immunity. Our data suggest that the context of gene expression markedly influences the T cell immunodominance hierarchy of CMV Ags, but the immune protection against HSV-1 does not require inflationary CD8 responses against the recombinant CMV-expressed epitope.
Affiliations:Department of Vaccinology, Helmholtz Center for Infection Research, Braunschweig 38124, Germany.
Reference Type:Literature
PubMed ID:23460738
Journal:J Immunol
Journal Volume:190
Article Pages:3399-409
Journal ISSN:1550-6606
Article Chemical List:Antigens, Viral;Epitopes, T-Lymphocyte;Immunodominant Epitopes;Peptides
Article MeSH List:Animals; Antigens, Viral(chemistry; genetics; immunology); CD8-Positive T-Lymphocytes(immunology); Disease Models, Animal; Epitopes, T-Lymphocyte(chemistry; immunology); Gene Expression; Gene Order; Genome, Viral; Herpes Simplex(immunology; prevention & control); Herpesvirus 1, Human(immunology); Immunodominant Epitopes(genetics; immunology); Male; Mice; Muromegalovirus(genetics; immunology); Mutation; Peptides(chemistry; genetics; immunology); Phenotype; Virus Replication
Curation Last Updated:2015-07-30 20:47:37