A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3⁺ T_reg cell development.

ABSTRACT: The neonatal thymus generates Foxp3⁺ regulatory T (tT_reg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tT_reg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tT_reg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IA^b-Padi4 with moderate dwell times within a conventional docking orientation are exported as tT_reg cells. In contrast

SUBMITTER: Stadinski BD 

PROVIDER: S-EPMC7039339 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature