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Quantification of repertoire diversity of influenza-specific epitopes with predominant public or private TCR usage
Journal article   Peer reviewed

Quantification of repertoire diversity of influenza-specific epitopes with predominant public or private TCR usage

Katherine Kedzierska, E Bridie Day, Jing Pi, Stephen B Heard, Peter C Doherty, Stephen J Turner and Stanley Perlman
Journal of immunology (Baltimore, Md. : 1950), Vol.177(10), pp.6705-6712
11/15/2006
DOI: 10.4049/jimmunol.177.10.6705
PMID: 17082583

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Abstract

The H-2Db-restricted CD8 T cell immune response to influenza A is directed at two well-described epitopes, nucleoprotein 366 (NP366) and acid polymerase 224 (PA224). The responses to the two epitopes are very different. The epitope NP366-specific response is dominated by TCR clonotypes that are public (shared by most mice), whereas the epitope PA224-specific response is private (unique within each infected animal). In addition to being public, the NP366-specific response is dominated by a few clonotypes, when T cell clonotypes expressing the Vbeta8.3 element are analyzed. Herein, we show that this response is similarly public when the NP366+Vbeta4+ CD8 T cell response is analyzed. Furthermore, to determine whether these features resulted in differences in total TCR diversity in the NP366+ and PA224+ responses, we quantified the number of different CD8 T clonotypes responding to each epitope. We calculated that 50-550 clonotypes recognized each epitope in individual mice. Thus, although the character of the response to the two epitopes appeared to be different (private and diverse vs public and dominated by a few clonotypes), similar numbers of precursor cells responded to both epitopes and this number was of similar magnitude to that previously reported for other viral CD8 T cell epitopes. Therefore, even in CD8 T cell responses that appear to be oligoclonotypic, the total response is highly diverse.
Lymphocytic choriomeningitis virus - immunology Cell Line Epitopes, T-Lymphocyte - biosynthesis Influenza A Virus, H3N2 Subtype - enzymology Epitopes, T-Lymphocyte - analysis Mice, Inbred C57BL RNA-Binding Proteins - immunology Influenza A Virus, H3N2 Subtype - immunology CD8-Positive T-Lymphocytes - enzymology Murine hepatitis virus - immunology Animals CD8-Positive T-Lymphocytes - virology Receptors, Antigen, T-Cell, alpha-beta - biosynthesis Dogs CD8-Positive T-Lymphocytes - metabolism Female Viral Core Proteins - immunology Clone Cells Mice Receptors, Antigen, T-Cell, alpha-beta - metabolism CD8-Positive T-Lymphocytes - immunology Epitopes, T-Lymphocyte - metabolism RNA Replicase - immunology Nucleoproteins - immunology

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