caa a22 4500 55524394X 20201130031324.0 cr unu---uuuuu 190205e20180713xx s 000 0 eng (BORIS)oai:boris.unibe.ch:122998 610 ddc Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells [Elektronische Daten] [Ales Drobek, Alena Moudra, Daniel Mueller, Martina Huranova, Veronika Horkova, Michaela Pribikova, Robert Ivanek, Susanne Oberle, Dietmar Zehn, Kathleen McCoy, Peter Draber, Ondrej Stepanek] publishedVersion openAccess eu-repo 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. Drobek Ales joint author Moudra Alena joint author Mueller Daniel joint author Huranova Martina joint author Horkova Veronika joint author Pribikova Michaela joint author Ivanek Robert joint author Oberle Susanne joint author Zehn Dietmar joint author McCoy Kathleen joint author Draber Peter joint author Stepanek Ondrej joint author The EMBO Journal Onlinezugriff via WWW text/html Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathleen; Draber, Peter; Stepanek, Ondrej (2018). Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells. The EMBO Journal, 37(14) EMBO Press 10.15252/embj.201798518 <http://dx.doi.org/10.15252/embj.201798518> BORIS BK010053 XK010053 XK010000 1 info:eu-repo/semantics/article boris PeerReviewed boris peerstatus BORIS BORIS BORIS info:eu-repo/semantics/article openAccess BORIS 856 42 Onlinezugriff via WWW text/html Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathleen; Draber, Peter; Stepanek, Ondrej (2018). Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells. The EMBO Journal, 37(14) EMBO Press 10.15252/embj.201798518 <http://dx.doi.org/10.15252/embj.201798518> BORIS 700 1- Drobek Ales joint author BORIS 700 1- Moudra Alena joint author BORIS 700 1- Mueller Daniel joint author BORIS 700 1- Huranova Martina joint author BORIS 700 1- Horkova Veronika joint author BORIS 700 1- Pribikova Michaela joint author BORIS 700 1- Ivanek Robert joint author BORIS 700 1- Oberle Susanne joint author BORIS 700 1- Zehn Dietmar joint author BORIS 700 1- McCoy Kathleen joint author BORIS 700 1- Draber Peter joint author BORIS 700 1- Stepanek Ondrej joint author BORIS 773 0- The EMBO Journal