Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections

Front Immunol. 2022 Oct 6;13:1009198. doi: 10.3389/fimmu.2022.1009198. eCollection 2022.


Mature T cells are selected for recognizing self-antigens with low to intermediate affinity in the thymus. Recently, the relative differences in self-reactivity among individual T-cell clones were appreciated as important factors regulating their fate and immune response, but the role of self-reactivity in T-cell biology is incompletely understood. We addressed the role of self-reactivity in T-cell diversity by generating an atlas of mouse peripheral CD8+ T cells, which revealed two unconventional populations of antigen-inexperienced T cells. In the next step, we examined the steady-state phenotype of monoclonal T cells with various levels of self-reactivity. Highly self-reactive clones preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing type I interferon-induced genes, showing that these two subsets have unrelated origins. The functional comparison of naïve monoclonal CD8+ T cells specific to the identical model antigen did not show any correlation between the level of self-reactivity and the magnitude of the immune response.

Keywords: T cell; T-cell diversity; antigen-inexperienced memory-like CD8 T cells; interferon response; self-reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens
  • CD8-Positive T-Lymphocytes*
  • Clone Cells
  • Interferon Type I*
  • Mice
  • Thymus Gland


  • Autoantigens
  • Interferon Type I