AUTHOR=Paprckova Darina , Niederlova Veronika , Moudra Alena , Drobek Ales , Pribikova Michaela , Janusova Sarka , Schober Kilian , Neuwirth Ales , Michalik Juraj , Huranova Martina , Horkova Veronika , Cesnekova Michaela , Simova Michaela , Prochazka Jan , Balounova Jana , Busch Dirk H. , Sedlacek Radislav , Schwarzer Martin , Stepanek Ondrej TITLE=Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1009198 DOI=10.3389/fimmu.2022.1009198 ISSN=1664-3224 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.