Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 4, Pages 1485-1490Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1323736111
Keywords
recall CD8(+) T-cell response; clonal selection; antiviral immunity; memory CD8(+) T cells; influenza virus
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Funding
- National Health and Medical Research Council (NHMRC) [AI628316, AI1046333]
- National Institute of Health [AI091938, AI107625]
- Sylvia and Charles Viertel Senior Medical Research fellowship
- NHMRC Biomedical Postgraduate Scholarship [ID520643]
- Australian Research Council Future Fellowship
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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) 3 alpha and CDR3 beta regions of individual T-cell 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 TCR alpha- and beta 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.
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