Epitopes described in "Memory CD8+ T cells specific for a single immunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease."

Article Authors:Sanda Remakus; Daniel Rubio; Xueying Ma; Alessandro Sette; Luis J Sigal
Article Title:Memory CD8+ T cells specific for a single immunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease.
Reference Detail
Reference ID:1025068
Abstract:The antigens recognized by individual CD8(+) T cells are small peptides bound to major histocompatibility complex (MHC) class I molecules. The CD8(+) T cell response to a virus is restricted to several peptides, and the magnitudes of the effector as well as memory phases of the response to the individual peptides are generally hierarchical. The peptide eliciting a stronger response is called immunodominant (ID), and those with smaller-magnitude responses are termed subdominant (SD). The relative importance of ID and SD determinants in protective immunity remains to be fully elucidated. We previously showed that multispecific memory CD8(+) T cells can protect susceptible mice from mousepox, an acute lethal viral disease. It remained unknown, however, whether CD8(+) T cells specific for single ID or SD peptides could be protective. Here, we demonstrate that immunization with dendritic cells pulsed with ID and some but not all SD peptides induces memory CD8(+) T cells that are fully capable of protecting susceptible mice from mousepox. Additionally, while natural killer (NK) cells are essential for the natural resistance of nonimmune C57BL/6 (B6) to mousepox, we show that memory CD8(+) T cells of single specificity also protect B6 mice depleted of NK cells. This suggests it is feasible to produce effective antiviral CD8(+) T cell vaccines using single CD8(+) T cell determinants and that NK cells are no longer essential when memory CD8(+) T cells are present.
Affiliations:Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA.
Reference Type:Literature
PubMed ID:22740418
Journal:J Virol
Journal Volume:86
Article Pages:9748-59
Journal ISSN:1098-5514
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@66002c5a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@155ffd07;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@50dce187;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@555a8f8a;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2c85d8cd;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@75c9191
Article MeSH List:Amino Acid Sequence; Animals; CD8-Positive T-Lymphocytes(immunology); Ectromelia virus(genetics; immunology); Ectromelia, Infectious(immunology; prevention & control; virology); H-2 Antigens(genetics; immunology); Immunization; Immunodominant Epitopes(genetics); Immunologic Memory; Killer Cells, Natural(immunology); Mice; Mice, Inbred C57BL; Peptides(genetics; immunology); Viral Proteins(genetics; immunology); Viral Vaccines(genetics; immunology)
Curation Last Updated:2015-01-18 00:29:55