UMass Chan Medical School Faculty Publications
Title
Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection
UMMS Affiliation
Department of Pathology
Publication Date
2013-01-02
Document Type
Article
Subjects
Adoptive Transfer; Animals; Antigens, Viral; CD4-Positive T-Lymphocytes; Cross Reactions; Cytokines; Homeodomain Proteins; Inhibitory Concentration 50; Lymphocyte Activation; Major Histocompatibility Complex; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell; Vaccinia; Vaccinia virus
Disciplines
Immunology and Infectious Disease | Immunopathology
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.
DOI of Published Version
10.1073/pnas.1208328110
Source
Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):288-93. doi: 10.1073/pnas.1208328110. Link to article on publisher's site
Related Resources
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
PubMed ID
23248307
Repository Citation
Vanguri V, Govern C, Smith R, Huseby E. (2013). Viral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection. UMass Chan Medical School Faculty Publications. https://doi.org/10.1073/pnas.1208328110. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/208