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

• Ales Drobek ^[2] ; Alena Moudra ^[2] ; Daniel Mueller ^[3] ; Martina Huranova ^[2] ; Veronika Horkova ^[2] ; Michaela Pribikova ^[2] ; Robert Ivanek ^[4] ; Susanne Oberle ^[1] ; Dietmar Zehn ^[1] ; Kathy D McCoy ^[5] ; Peter Draber ^[2] ; Ondrej Stepanek ^[6]
  1. [1] Swiss Vaccine Research Institute

     Swiss Vaccine Research Institute

     Lausana, Suiza

     
  2. [2] 1 Laboratory of Adaptive Immunity Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic
  3. [3] 2 Department of Biomedicine University Hospital and University of Basel Basel Switzerland
  4. [4] 2 Department of Biomedicine University Hospital and University of Basel Basel Switzerland; 3 Swiss Institute of Bioinformatics Basel Switzerland
  5. [5] 6 Department of Clinical Research (DKF) Inselspital University of Bern Bern Switzerland; 8Present address: Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary Calgary AB Canada
  6. [6] 1 Laboratory of Adaptive Immunity Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic; 2 Department of Biomedicine University Hospital and University of Basel Basel Switzerland

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 14, 2018, págs. 5-5
• Idioma: inglés
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  • 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.