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

T Cukalac, J Chadderton, A Handel… - Proceedings of the …, 2014 - National Acad Sciences
T Cukalac, J Chadderton, A Handel, PC Doherty, SJ Turner, PG Thomas, NL La Gruta
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
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 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.
National Acad Sciences