Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

To characterize the nature ofthyroid peroxidase(TPO)autoantibodies present in the sera of patients with autoimmune thyroid disease, we cloned three IgGl/kappa Fab fragments which bind 125I-TPO. This was accomplished by the molecular cloning and expression in bacteria ofIgG gene fragments from B cells infiltrating the thyroid ofa patient with Graves' disease. The three Fab fragments (SP2, SP4, and SP5) are coded for by a common heavy chain (VH1, D, JH3) and three related, but different, light chains (VK1, JK2). TheSPFab fragments bind specifically to TPO with high affinities (6 x 10-l"-2 X 10`' M) comparable to those of serum TPO autoantibodies. TPO autoantibodies represented by the SP Fab fragments are present in all 11 patients studied, constitute a high proportion (3672%) of serum TPO autoantibodies in individual patients and interact with a conformational epitope on TPO. (J. Clin. Invest. 1992. 90:720-726.) Key words: thyroid peroxidase * autoantibody - epitope * autoimmunity