HUMAN MONOCLONAL ISLET-SPECIFIC AUTOANTIBODIES SHARE FEATURES OF ISLET-CELL AND 64 KDA ANTIBODIES

The first human monoclonal islet cell antibodies of the IgG class (MIC A 1-6) obtained from an individual with Type 1 (insulin-dependent) dia betes mellitus were cytoplasmic islet cell antibodies selected by the indirect immunofluorescence test on pancreas sections. Surprisingly, t hey all recognized the 64 kDa autoantigen glutamate decarboxylase. In this study we investigated which typical features of cytoplasmic islet cell antibodies are represented by these monoclonals. We show by doub le immunofluorescence testing that MICA 1-6 stain pancreatic beta cell s which is in agreement with the beta-cell specific expression of glut amate decarboxylase. In contrast an islet-reactive IgM monoclonal anti body obtained from a pre-diabetic individual stained all islet cells b ut lacked the tissue specificity of MICA 1-6 and must therefore be con sidered as a polyreactive IgM-antibody. We further demonstrate that MI CA 1-6 revealed typical features of epitope sensitivity to biochemical treatment of the target tissue which has been demonstrated for islet cell antibodies, and which has been used to argue for a lipid rather t han a protein nature of target antigens. Our results provide direct ev idence that the epitopes recognized by the MICA are destroyed by metha nol/chloroform treatment but reveal a high stability to Pronase digest ion compared to proinsulin epitopes. Conformational protein epitopes i n glutamate decarboxylase therefore show a sensitivity to biochemical treatment of sections such as ganglioside epitopes. MICA 1-6 share typ ical features of islet cell and 64 kDa antibodies and reveal that glut amate decarboxylase-reactive islet cell antibodies represent a subgrou p of islet cell antibodies present in islet cell antibody-positive ser a.