Infection with group A Streptococcus (GAS) causes the common and treatable pharyngitis known as strep throat; however, these infections are also associated with autoimmune diseases of the central nervous system (CNS). A subset of children are at risk of developing pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), which are characterized by an abrupt onset of abnormal behaviors. In murine models, GAS has been shown to induce a robust Th17 response in nasal-associated lymphoid tissues. In this episode, Pat Cleary and Dritan Agalliu discuss their collaboration to investigate the link between the generation of GAS-specific Th17 cells and CNS autoimmunity. They determined that multiple intranasal GAS challenges in mice promotes migration and persistence of GAS-specific Th17 cells to the brain, leading to blood-brain barrier (BBB) breakdown and autoantibody access to the CNS. Moreover, they identified GAS-specific Th17 cells in the tonsils of patients naturally exposed to GAS. Together, these data provide insights into the immunopathology underlying GAS-associated neurological complications.