Influenza epitope-specific CD8+ T cell avidity, but not cytokine polyfunctionality, can be determined by tcrβ clonotype

Jessica M Moffat, Andreas Handel, Peter C Doherty, Stephen J. Turner, Paul G. Thomas, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Cytokine polyfunctionality has recently emerged as a correlate of effective CTL immunity to viruses and tumors. Although the determinants of polyfunctionality remain unclear, there are published instances of a link between the productionof multiple effector molecules and the peptide plus MHC class I molecule avidity of T cell populations. Influenza A virus infection of C57BL/6J mice induces CTL populations specific for multiple viral epitopes, each with varying proportions of monofunctional (IFN-γ+ only) or polyfunctional (IFN-γ+TNF-α+IL-2+) CTLs. In this study, we probe the link between TCR avidity and polyfunctionality for two dominant influenza epitopes (DbNP366 and D bPA224) by sequencing the TCR CDR3b regions of influenza-specific IFN-γ+ versus IFN-γ+IL- 2+ cells, or total tetramer+ versus high-avidity CTLs (as defined by the peptide plus MHC class I molecule-TCR dissociation rate). Preferential selection for particular clonotypes was evident for the high-avidity DbPA224-specific set but not for any of the other subsets examined. These data suggest that factors other than TCRβ sequence influence cytokine profiles and demonstrate no link between differential avidity and polyfunctionality.

Original languageEnglish
Pages (from-to)6850-6856
Number of pages7
JournalJournal of Immunology
Volume185
Issue number11
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

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