Self-reactivity of CD8 T-cell clones determines their differentiation status rather than their responsiveness in infections
Darina Paprčková, Veronika Niederlová, Alena Moudrá, Ales Drobek, Michaela Přibíková, Sarka Janusova, Kilian Schober, Aleš Neuwirth, Juraj Michálik, Martina Huranová, Veronika Horková, Michaela Cesnekova, Michaela Simova, Jan Procházka, Jana Balounová, Dirk H. Busch, Radislav Sedláček, Martin Schwarzer, Ondřej Štěpánek
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.