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

Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1485-90. doi: 10.1073/pnas.1323736111. Epub 2014 Jan 13.


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 T-cell receptor (TCR) heterodimers, we characterized the antigen-driven 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.

Keywords: antiviral immunity; clonal selection; influenza virus; memory CD8+ T cells; recall CD8+ T-cell response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Affinity*
  • CD8-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • Female
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / complications
  • Orthomyxoviridae Infections / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Reproducibility of Results


  • Receptors, Antigen, T-Cell, alpha-beta