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

Darina Paprckova, Veronika Niederlova, Alena Moudra, Ales Drobek, Michaela Pribikova, Sarka Janusova, Kilian Schober, Ales Neuwirth, Juraj Michalik, Martina Huranova, Veronika Horkova, Michaela Cesnekova, Michaela Simova, Jan Prochazka, Jana Balounova, Dirk H. Busch, Radislav Sedlacek, Martin Schwarzer, Ondrej Stepanek*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1009198
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 6 Oct 2022
Externally publishedYes

Keywords

  • T cell
  • T-cell diversity
  • antigen-inexperienced memory-like CD8 T cells
  • interferon response
  • self-reactivity

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