Molecular Recognition of Human Insulin Receptor by Autoantibodies in a Human Serum

Abstract
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 α-subunit of HIR was examined by radioimmuno-adsorbent titrations. Autoantibodies were bound by two of these peptides, namely α277-299 and α705-731, 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 α277-299 and α705-731 contain autoantigenic sites of HIR. In addition, region α655-670 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.