Changes to peptide structure, not concentration, contribute to expansion of the lowest avidity cytotoxic T lymphocytes

Journal of Leukocyte Biology
Graham R LeggattIan H Frazer

Abstract

The efficient in vitro expansion of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) for use in adoptive immunotherapy represents an important clinical goal. Furthermore, the avidity of expanded CTL populations often correlates closely with clinical outcome. In our study, high-avidity CTL lines could be expanded ex vivo from an antigen-primed animal using low peptide concentration, and intermediate peptide concentrations favored the generation of lower avidity CTL. Further increases in peptide concentration during culture inhibited the expansion of all peptide-specific CD8+ cells. In contrast, a single amino acid variant peptide efficiently generated functional CTL populations at high or low peptide concentration, which responded to wild-type epitope with the lowest average avidity seen in this study. We propose that for some peptides, the efficient generation of low-avidity CTL responses will be favored by stimulation with altered peptide rather than high concentrations of wild-type epitope. In addition, some variant peptides designed to have improved binding to major histocompatibility complex class I may reduce rather than enhance the functional avidity for the wild-type peptide of ex vivo-expanded CTL. These observations...Continue Reading

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Citations

Nov 5, 2014·PloS One·Michelle A NellerChristopher W Schmidt
Jul 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen R MattarolloIan H Frazer
Nov 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Salvatore FiorenzaIan H Frazer

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