In vivo persistence of codominant human CD8+ T cell clonotypes is not limited by replicative senescence or functional alteration

Laurent Derré, Marc Bruyninx, Petra Baumgaertner, Estelle Devevre, Patricia Corthesy, Cédric Touvrey, Yolanda D. Mahnke, Hanspeter Pircher, Verena Voelter, Pedro Romero, Daniel E. Speiser, Nathalie Rufer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

T cell responses to viral epitopes are often composed of a small number of codominant clonotypes. In this study, we show that tumor Ag-specific T cells can behave similarly. In a melanoma patient with a long lasting HLA-A2/NY-ESO-1-specific T cell response, reaching 10% of circulating CD8 T cells, we identified nine codominant clonotypes characterized by individual TCRs. These clonotypes made up almost the entire pool of highly differentiated effector cells, but only a fraction of the small pool of less differentiated "memory" cells, suggesting that the latter serve to maintain effector cells. The different clonotypes displayed full effector function and expressed TCRs with similar functional avidity. Nevertheless, some clonotypes increased, whereas others declined in numbers over the observation period of 6 years. One clonotype disappeared from circulating blood, but without preceding critical telomere shortening. In turn, clonotypes with increasing frequency had accelerated telomere shortening, correlating with strong in vivo proliferation. Interestingly, the final prevalence of the different T cell clonotypes in circulation was anticipated in a metastatic lymph node withdrawn 2 years earlier, suggesting in vivo clonotype selection driven by metastases. Together, these data provide novel insight in long term in vivo persistence of T cell clonotypes associated with continued cell turnover but not replicative senescence or functional alteration.

Original languageEnglish (US)
Pages (from-to)2368-2379
Number of pages12
JournalJournal of Immunology
Volume179
Issue number4
DOIs
StatePublished - Aug 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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