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Current treatment of autoimmune disease usually involves the use of cytotoxic drugs or biologic agents that interfere with the activity of B cells, T cells or key cytokines, such as TNF, IL-1 and IL-6. On occasion, polyclonal immunoglobulin G (IgG), intravenous (IVIg) is used. The discovery of IgG- (and hence IVIg-) derived T regulatory (Treg) epitopes that trigger the expansion of Tregs in vitro and in vivo provides a novel explanation for the effect of IVIg. These IgG-derived Treg epitopes (also known as Tregitopes) appear to be effective on their own (in vivo, in autoimmune disease models) and when co-administered with a specific autoimmune disease antigen, contribute to antigen-specific tolerance induction. A description of Tregitopes and a brief discussion of their potential applications in autoimmune disease are provided here. Tregitope-based immunotherapy has the potential to modify the current autoimmune pharmacopeia.