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Strong homeostatic TCR signals induce formation of self‐tolerant virtual memory CD8 T cells
Author(s) -
Drobek Ales,
Moudra Alena,
Mueller Daniel,
Huranova Martina,
Horkova Veronika,
Pribikova Michaela,
Ivanek Robert,
Oberle Susanne,
Zehn Dietmar,
McCoy Kathy D,
Draber Peter,
Stepanek Ondrej
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798518
Subject(s) - biology , t cell receptor , microbiology and biotechnology , homeostasis , self tolerance , cytotoxic t cell , biophysics , t cell , immune system , genetics , in vitro
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.