Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope
AuthorKedzierska, K; Turner, SJ; Doherty, PC
Source TitleProceedings of the National Academy of Sciences of USA
PublisherNATL ACAD SCIENCES
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsKedzierska, K., Turner, S. J. & Doherty, P. C. (2004). Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101 (14), pp.4942-4947. https://doi.org/10.1073/pnas.0401279101.
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC387353
C1 - Journal Articles Refereed
The CD8+ T cell response to the immunodominant DbNP366 epitope has been analyzed sequentially to determine the prevalence and persistence of different T cell antigen receptor (TCR)Vbeta8.3 clonotypes after primary and secondary influenza virus challenge. Based on the length and amino acid sequences of the complementarity-determining region 3 of TCRbeta (CDR3beta) loop and associated Jbeta usage, the same dominant TCRbeta signatures were found in the blood, the spleen, and the site of virus-induced pathology in the infected respiratory tract. Longitudinal analysis demonstrated that TCRbeta prominent in the antigen-driven phase of response persisted into memory and were again expanded after secondary challenge. A proportion of these high-frequency TCRbeta expressed "public" CDR3beta sequences that were detected in every mouse sampled, whereas others were found more than once but were not invariably present. Analysis of N-region nucleotide diversity established that as many as 10 different nucleic acid sequences (maximum of four "nucleotypes" in any one mouse) could encode a single public TCRbeta amino acid sequence. Conversely, whereas some of the unique, "private" TCRbeta achieved a substantial clone size, they were always specified by a single nucleotype. Although there is a strong stochastic element in this response, the public TCRbeta seem to represent a "best fit" for this immunodominant epitope, are selected preferentially from the naive TCR repertoire, and assume even greater prominence after secondary challenge.
KeywordsCellular Immunology; Immune System and Allergy
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