Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection

Tania Cukalac, Jesseka Chadderton, Andreas Handel, Peter C. Doherty, Stephen J. Turner, Paul G. Thomas, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

The recall of memory CD8+ cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual Tcell receptor (TCR) heterodimers, we characterized the antigendriven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα? and β chain-dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity.

Original languageEnglish
Pages (from-to)1485-1490
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number4
DOIs
Publication statusPublished - 28 Jan 2014
Externally publishedYes

Keywords

  • Antiviral immunity
  • Clonal selection
  • Influenza virus
  • Memory CD8+ T cells
  • Recall CD8+ T-cell response

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