In this graduate school of Tokyo Medical and Dental University, I was given a somewhat vague but farsighted theme by a professor: "protein-DNA interaction." Within these simple words, I was given a free hand. Being curious about the etiology of connective tissue diseases, I began to study the biochemistry and pathophysiology of autoimmunity, especially the nature of anti-DNA antibodies that are the principal anti-nuclear antibodies observed in patients with systemic lupus erythematosus (SLE). My thesis was on the characterization of serum anti-DNA antibodies purified by a novel method of affinity column chromatography. Thereafter, I remained involved in this fascinating field. In spite of the rapid progress in molecular immunology, the etiology of any particular systemic autoimmune disorder remains elusive at this point. Here, works on a monoclonal anti-DNA antibody performed in the laboratories of Dr. B. D. Stollar (Tufts University, Boston), Dr. Y. Kanai (University of Tokyo), and in our laboratory will be reviewed along with related articles.