University of Massachusetts 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

1-2-2013

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.

Rights and Permissions

Citation: 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

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

23248307