tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1485-90. doi: 10.1073/pnas.1323736111. Epub 2014 Jan 13.
Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection.
Cukalac T, Chadderton J, Handel A, Doherty PC, Turner SJ, Thomas PG, La Gruta NL.
Author information
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 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
PMID:
24474775
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24474775
Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection.
Cukalac T, Chadderton J, Handel A, Doherty PC, Turner SJ, Thomas PG, La Gruta NL.
Author information
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 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
PMID:
24474775
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24474775