NEW MONOCLONAL-ANTIBODY DIAGNOSTIC REAGENTS FOR TYPE-I DIABETES - DIFFERENTIAL LYMPHOCYTE SURFACE-ANTIGEN EXPRESSION RELATED TO DISEASE

New cellular-based reagents are needed to diagnose type I diabetes as well as to monitor the outcomes of clinical trials at early time point s. Four new monoclonal antibodies (mAbs) have been shown to demonstrat e reduced binding to lymphocytes from identical twins with long-term t ype I diabetes relative to that observed with lymphocytes from their t win partners without diabetes or from control subjects, Biochemical an alysis revealed mAb 3G12EG recognized an unidentified 45-kDa protein, whereas mAb 2E8F1 and 5B6E11 did not appear to precipitate specific pr oteins as detected by SDS-PAGE. Electrophoresis under reducing and non reducing conditions and peptide mapping revealed that mAb 8F410 recogn izes a novel dimeric form of HLA class I molecule. Predictions from cr ystallography studies suggested previously this class I dimer as the o ptimal activation of a single CD8 T-cell. In B-cells from both normal and diabetic individuals, the class I dimer was minimally associated w ith beta(2)-microglobulin rapidly formed in the endoplasmic reticulum. These new reagents appear to be able to identify new lymphocyte surfa ce phenotypes associated with diabetes expression in both fresh blood samples and Epstein-Barr virus-established cell lines.