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


ABSTRACT: 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.

SUBMITTER: Drobek A 

PROVIDER: S-EPMC6043851 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Drobek Ales A   Moudra Alena A   Mueller Daniel D   Huranova Martina M   Horkova Veronika V   Pribikova Michaela M   Ivanek Robert R   Oberle Susanne S   Zehn Dietmar D   McCoy Kathy D KD   Draber Peter P   Stepanek Ondrej O  

The EMBO journal 20180511 14


Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8<sup>+</sup> 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 de  ...[more]

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