Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells

Ales Drobek, Alena Moudra, Daniel Mueller, Martina Huranova, Veronika Horkova, Michaela Pribikova, Robert Ivanek, Susanne Oberle, Dietmar Zehn, Kathy D. McCoy, Peter Draber, Ondrej Stepanek

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10–20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity.

Original languageEnglish
Article numbere98518
JournalEMBO Journal
Issue number14
StatePublished - 13 Jul 2018


  • T-cell receptor repertoire
  • gene expression profiling of T-cell subsets
  • retrogenic T cell
  • self-reactivity
  • virtual memory T cells


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