Reproducible selection of high avidity CD8+ T-cell clones following secondary acute virus infection.
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.
Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia.
Tania
T
Cukalac
Jesseka
J
Chadderton
Andreas
A
Handel
Peter C
PC
Doherty
Stephen J
SJ
Turner
Paul G
PG
Thomas
Nicole L
NL
La Gruta
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015203:Reproducibility of Results
D016693:Receptors, Antigen, T-Cell, alpha-beta
antiviral immunity; clonal selection; influenza virus; memory CD8+ T cells; recall CD8+ T-cell response