Epitopes described in "Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection."

Article Authors:Vijay Vanguri; Christopher C Govern; Rebecca Smith; Eric S Huseby
Article Title:Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection.
Reference Detail
Reference ID:1025408
Abstract:T-cell recognition of ligands is polyspecific. This translates into antiviral T-cell responses having a range of potency and specificity for viral ligands. How these ligand recognition patterns are established is not fully understood. Here, we show that an activation threshold regulates whether robust CD4 T-cell activation occurs following viral infection. The activation threshold was variable because of its dependence on the density of the viral peptide (p)MHC displayed on infected cells. Furthermore, the activation threshold was not observed to be a specific equilibrium affinity (K(D)) or half-life (t(1/2)) of the TCR-viral pMHC interaction, rather it correlated with the confinement time of TCR-pMHC interactions, i.e., the half-life (t(1/2)) of the interaction accounting for the effects of TCR-pMHC rebinding. One effect of a variable activation threshold is to allow high-density viral pMHC ligands to expand CD4 T cells with a variety of potency and peptide cross-reactivity patterns for the viral pMHC ligand, some of which are only poorly activated by infections that produce a lower density of the viral pMHC ligand. These results argue that antigen concentration is a key component in determining the pattern of K(D), t(1/2) and peptide cross-reactivity of the TCRs expressed on CD4 T cells responding to infection.
Affiliations:Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Reference Type:Literature
PubMed ID:23248307
Journal:Proc Natl Acad Sci U S A
Journal Volume:110
Article Pages:288-93
Journal ISSN:0027-8424
Article Chemical List:Antigens, Viral;Cytokines;Homeodomain Proteins;Receptors, Antigen, T-Cell;RAG-1 protein
Article MeSH List:Adoptive Transfer; Animals; Antigens, Viral(metabolism); CD4-Positive T-Lymphocytes(immunology); Cross Reactions(immunology); Cytokines(metabolism); Homeodomain Proteins(genetics); Inhibitory Concentration 50; Lymphocyte Activation(immunology); Major Histocompatibility Complex(immunology); Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell(immunology; metabolism); Vaccinia(immunology); Vaccinia virus(immunology)
Curation Last Updated:2015-07-30 20:46:51