HLA-DR-RESTRICTED T-CELL LINES FROM NEWLY-DIAGNOSED TYPE-1 DIABETIC-PATIENTS SPECIFIC FOR INSULINOMA AND NORMAL ISLET BETA-CELL PROTEINS - LACK OF REACTIVITY TO GLUTAMIC-ACID DECARBOXYLASE

T cells reacting with pancreatic islet beta cell proteins play a pivot al role in the pathogenesis of type 1 diabetes in experimental animal models and man, although the islet cell autoantigens against which the se T cells are directed remain to be characterized. We have previously shown the presence of disease-related antigens residing in the transp lantable RM insulinoma membranes which are recognized by T cells from diabetic NOD mice. We now report on the establishment of CD4(+), T cel l lines reacting with insulinoma membranes from six newly diagnosed ty pe 1 diabetic patients. Detailed examination of T cell lines from two patients revealed that both the lines continued to react with normal i slet cell proteins and, interestingly, were also stimulated by antigen s present in brain microsomes. The two T cell lines showed reactivity with different molecular weight proteins of the insulinoma membranes a nd both the lines were histocompatibility-linked antigen (HLA)-DR rest ricted. Although the insulinoma membrane preparation is known to conta in glutamic acid decarboxylase (GAD), none of the six T cell lines pro liferates in response to purified GAD. These T cell lines will be valu able in characterizing novel islet beta cell antigens which are likely to be implicated in type 1 diabetes.