Viral Infection Triggers Central Nervous System Autoimmunity Via Activation of Dual TCR-Expressing CD8(+) T Cells

Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause a breakdown of myelin-specific T cell tolerance are unknown. We found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance can be broken and autoimmunity induced by infection with a virus that does not express MBP cross-reactive epitopes and does not depend on bystander activation. Instead, the virus activated dual T cell receptor (TCR)-expressing T cells capable of recognizing both MBP and viral antigens. These results demonstrate the importance of dual TCR T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected individuals, as hypothesized in the etiology of MS.