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dc.contributor.authorVanguri, Vijay
dc.contributor.authorGovern, Christopher
dc.contributor.authorSmith, Rebecca
dc.contributor.authorHuseby, Eric
dc.date2022-08-11T08:08:28.000
dc.date.accessioned2022-08-23T15:55:59Z
dc.date.available2022-08-23T15:55:59Z
dc.date.issued2013-01-02
dc.date.submitted2013-07-25
dc.identifier.citationProc Natl Acad Sci U S A. 2013 Jan 2;110(1):288-93. doi: 10.1073/pnas.1208328110. <a href="http://dx.doi.org/10.1073/pnas.1208328110">Link to article on publisher's site</a>
dc.identifier.issn0027-8424 (Linking)
dc.identifier.doi10.1073/pnas.1208328110
dc.identifier.pmid23248307
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29873
dc.description.abstractT-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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23248307&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1073/pnas.1208328110
dc.subjectAdoptive Transfer
dc.subjectAnimals
dc.subjectAntigens, Viral
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectCross Reactions
dc.subjectCytokines
dc.subjectHomeodomain Proteins
dc.subjectInhibitory Concentration 50
dc.subjectLymphocyte Activation
dc.subjectMajor Histocompatibility Complex
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectReceptors, Antigen, T-Cell
dc.subjectVaccinia
dc.subjectVaccinia virus
dc.subjectImmunology and Infectious Disease
dc.subjectImmunopathology
dc.titleViral antigen density and confinement time regulate the reactivity pattern of CD4 T-cell responses to vaccinia virus infection
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume110
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/208
dc.identifier.contextkey4349485
html.description.abstract<p>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.</p>
dc.identifier.submissionpathfaculty_pubs/208
dc.contributor.departmentDepartment of Pathology
dc.source.pages288-93


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