The anti-insulin trimolecular complex in type 1 diabetes

Description of the immunologic components needed for autoimmune diabetes.

The major histocompatability complex (MHC) class II molecules are the primary susceptibility genes for many autoimmune diseases, including type 1 diabetes. Understanding of the structural interaction between MHC molecules, antigenic peptides, and T-cell receptors (the three components of the trimolecular complex) has increased greatly over the past several years. The components of the anti-insulin trimolecular complex and findings that insulin is a key autoantigen in type 1 diabetes are reviewed.

The anti-insulin trimolecular complex is well defined in the nonobese diabetic mouse model. Insulin and specifically, the amino acid sequence 9 to 23 of the insulin B chain, represents a primary antigenic target for islet autoimmunity in the nonobese diabetic mouse model of type 1 diabetes with a specific mutation of this peptide preventing all diabetes. Initial studies suggest the human homologs of the anti-insulin trimolecular complex may be relevant in human disease.