A virus-specific CD8(+) T cell immunodominance hierarchy determined by antigen dose and precursor frequencies
AuthorLa Gruta, NL; Kedzierska, K; Pang, K; Davenport, M; Chen, WS; Turner, SJ; Doherty, PC
Source TitleProceedings of the National Academy of Sciences of USA
PublisherNATL ACAD SCIENCES
University of Melbourne Author/sLa Gruta, Nicole; Kedzierska, Katherine; Turner, Stephen; Doherty, Peter
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsLa 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. https://doi.org/10.1073/pnas.0510429103.
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1348014
NHMRC Grant codeNHMRC/350395
C1 - Journal Articles Refereed
Immunodominance 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.
KeywordsCellular Immunology; Immune System and Allergy
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