DNA is a complex macromolecule whose immunological properties vary with base sequence and backbone structure. Although now recognized as important for normal immunity, the antigenic and immunogenic properties of DNA were originally conceptualized entirely in the context of systemic lupus erythematosus (SLE). This prototypic autoimmune disease is characterized by the production of antibodies to DNA (anti-DNA). These antibodies occur prominently in the sera of lupus patients and serve as markers of diagnosis and prognosis. The close association of anti-DNA with SLE has suggested that elucidating this response would provide fundamental insights into the mechanisms of autoimmunity, as opposed to normal responses (1).