Understanding why some individuals develop autoimmunity but others do not has long puzzled researchers. The culprits appear to be immune cells that bear two distinct recognition receptors according to a report published this week in Nature Immunology.
T cells, a component of the immune system, express surface receptors called TCRs that can recognize protein fragments displayed on target cell surfaces. Each T cell expresses a unique TCR that possesses a unique specificity. Joan Goverman and colleagues show some CD8+ T cells express two different TCRs: one specific for a viral peptide but a second that recognizes a brain-specific myelin peptide. Mice that possess these dual-TCR-expressing T cells infected with virus develop autoimmune encephalomyelitis, a model for the human disease multiple sclerosis.
Importantly, the scientists rule out previously suspected reasons for why viral infection triggers autoimmunity. The viral-specific TCR activates the T cell, which then circulates through the body seeking out virally infected cells to destroy and these armed T cells attack myelin-expressing cells through recognition by their second TCR.
Although Goverman and colleagues look at how viral infection triggers encephalomyelitis, their results might also explain how other autoimmune diseases are triggered.