A MULTIPLICITY OF PROTEIN ANTIGENS IN SUBCELLULAR-FRACTIONS OF RAT INSULINOMA TISSUE ARE ABLE TO STIMULATE T-CELLS OBTAINED FROM NONOBESE DIABETIC MICE

Type I (insulin-dependent) diabetes mellitus is a T-cell mediated auto immune disease with a number of different proteins being implicated as target autoantigens. A 38 kDa protein residing in the insulin secreto ry granule of insulinoma tissue is recognized by T-cell clones from a newly-diagnosed Type I diabetic patient. We have investigated the capa city of normal rat pancreatic beta-cell extracts and various subcellul ar fractions of transplantable RIN tissue to induce proliferation of T cells from non-obese diabetic (NOD) mice and H-2 identical NON - NOD- H-2g7 control mice. Normal rat islet beta-cell protein fractions induc ed intense, dose-dependent proliferation of NOD splenic T cells, but o nly marginal proliferative responses of NON-NOD-H-2g7 splenic T cells. To further localize the target antigens, four different subcellular f ractions from RIN tissue were used as a source of antigen; here in par ticular the cytosolic proteins showed dose-dependent activation capaci ty with splenic T cells in NOD animals. These activities were absent i n control mice. There was no proliferation after incubation with micro some preparations from other rat endocrine tissues. Purified carboxype ptidase H did not have any stimulatory activity on NOD T cells. Fracti onation of the RIN cytosolic proteins showed a large number of differe nt fractions eliciting proliferative activity. These results demonstra te that NOD T cells respond to a large number of potential islet beta- cell target antigens and it will be necessary to utilize NOD T-cell cl ones to identify the number and nature of these antigens.