Molecular recognition of human insulin receptor by autoantibodies in a human serum

Immune IgG was obtained from a patient's serum with autoantibodies against human insulin receptor (HIR). The binding activity of these autoantibodies to seven synthetic peptides of the alpha-subunit of HIR was examined by radioimmuno-adsorbent titrations. Autoantibodies were bound by two of these peptides, namely alpha 277-299 and alpha 705-731, and this binding was not inhibited by a very large (1,000 x) molar excess of normal human IgG. Furthermore, none of the peptides exhibited any binding activity towards 125I-labelled normal human IgG. Therefore, it was concluded that the regions alpha 277-299 and alpha 705-731 contain autoantigenic sites of HIR. In addition, region alpha 655-670 might constitute a minor antigenic site of HIR. Localization of these autoantigenic sites will permit the molecular investigation of the insulin-like activity of anti-HIR autoantibodies.