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dc.contributor.authorLa Gruta, NL
dc.contributor.authorKedzierska, K
dc.contributor.authorPang, K
dc.contributor.authorDavenport, M
dc.contributor.authorChen, WS
dc.contributor.authorTurner, SJ
dc.contributor.authorDoherty, PC
dc.identifierpii: 0510429103
dc.identifier.citationLa Gruta, N. L., Kedzierska, K., Pang, K., Davenport, M., Chen, W. S., Turner, S. J. & Doherty, P. C. (2006). A virus-specific CD8(+) T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 103 (4), pp.994-999.
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractImmunodominance hierarchies are a substantial, but poorly understood, characteristic of CD8(+) T cell-mediated immunity. Factors influencing the differential responses to the influenza A virus nucleoprotein (NP(366-374)) and acid polymerase (PA(224-233)) peptides presented by H2D(b) have been analyzed by disabling (N5--> Q substitution) these peptides in their native configuration, then expressing them in the viral neuraminidase protein. This strategy of shifting epitopes within the same viral context resulted in an apparent equalization of D(b)NP(366) [epitope consisting of viral nucleoprotein (NP) amino acid residues 366-374 complexed with the H2D(b) MHC class I glycoprotein] and D(b)PA(224) (H2D(b)+PA(224-233)) epitope abundance after direct infection in vitro and induced reproducible changes in the magnitude of the D(b)NP(366)- and D(b)PA(224)-specific T cell subsets generated after infection of mice. Comparison of D(b)NP(366)- and D(b) PA(224)-specific CD8(+) T cell responses induced from the native configuration and from the viral neuraminidase stalk demonstrated that the size of both primary and secondary responses is influenced by relative epitope levels and that, at least after secondary challenge, the magnitude of responses is also determined by CD8(+) T cell precursor frequency. Thus, this immunodominance hierarchy is a direct function of antigen dose and T cell numbers.
dc.subjectCellular Immunology; Immune System and Allergy
dc.titleA virus-specific CD8(+) T cell immunodominance hierarchy determined by antigen dose and precursor frequencies
dc.typeJournal Article
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMicrobiology And Immunology
melbourne.source.titleProceedings of the National Academy of Sciences of USA
melbourne.contributor.authorLa Gruta, Nicole
melbourne.contributor.authorKedzierska, Katherine
melbourne.contributor.authorTurner, Stephen
melbourne.contributor.authorDoherty, Peter
melbourne.identifier.fundernameidNHMRC, 350395
melbourne.accessrightsAccess this item via the Open Access location

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