Inducement of antibody that mimics insulin action on insulin receptor by insulin autoantibody directed at determinant at asparagine site on human insulin B chain.
We previously showed that purified human IgG1 insulin autoantibody (IAA) from the serum of male patient T.H. with insulin autoimmune syndrome is directed at a determinant at the asparagine site on the human insulin B chain. An anti-idiotypic antibody (anti-TH) that inhibited TH-IAA binding to human insulin was obtained by immunizing BALB/c mice with TH-IAA. Anti-TH bound to viable IM-9 cells and the purified insulin receptor from IM-9 cells. Anti-TH binding to IM-9 cells and the insulin receptor was inhibited by TH-IAA but not by human IgG. Moreover, incubation of HepG2 cells with anti-TH had an inhibitory effect on insulin binding to HepG2 cells. Anti-TH, like insulin, stimulated amino acid uptake in HepG2 cells. These findings indicate that the conformation of TH-IAA idiotope is a mirror image of the determinant on the insulin B chain, the binding site for TH-IAA on anti-TH is also related to the insulin binding site on the insulin receptor, and anti-TH mimics insulin action on the insulin receptor.
Uchigata
Y
Y
Diabetes Centre, Tokyo Women's Medical College, Japan.
Takayama-Hasumi
S
S
Kawanishi
K
K
Hirata
Y
Y
D000621:Aminoisobutyric Acids / Q000378:metabolism; D001216:Asparagine; D001323:Autoantibodies / Q000276:immunology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007328:Insulin / Q000276:immunology* / Q000494:pharmacology; D007330:Insulin Antibodies / Q000276:immunology*; D046911:Macromolecular Substances; D008297:Male; D011972:Receptor, Insulin / Q000276:immunology*
D000621:Aminoisobutyric Acids; D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007328:Insulin; D007330:Insulin Antibodies; D046911:Macromolecular Substances; C100049:2-aminoisobutyric acid; D001216:Asparagine; D011972:Receptor, Insulin