Purified human insulin autoantibody (IAA) collected from the serum of a man (T.H.) with insulin autoimmune syndrome was characterized. The TH-IAA was found to be of IgG1 (λ-light-chain) subclass. In addition to the single-binding affinity of TH-IAA to human insulin that we have shown in previous studies, the TH-IAA binding to human insulin was completely inhibited by a mouse monoclonal anti-idiotypic antibody against TH-IAA. A competitive inhibition study with various insulins revealed an epitope of human insulin against TH-IAA. These findings suggest that TH-IAA is monoclonal and is directed at a determinant at B-3 (asparagine) on the human insulin B-chain.

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