An islet-specific CD8(+) T cell hybridoma generated from non-obese diabetic mice recognizes insulin as an autoantigen

Although CD8(+) T cells play a major role in beta cell destruction in insul in-dependent diabetes in the non-obese diabetic mouse, the T cell autoantig en(s) recognized by such cells remains to be identified. Therefore, an isle t-reactive, CD8(+) T cell line was generated from islet-infiltrating cells and hybridized by fusion with a CD8(+) alpha beta TCR(-)BW5147 thymoma. In the presence of islets, none of the 12 CD3(+)CD8(+) T cell hybridomas isola ted secreted IL-2/IL-4 or IFN gamma but three were islet specific, as shown by activation induced cell death. Subclone 4A7.7.15 recognized only islets expressing H-2K(d), demonstrated islet-specific inhibition of proliferatio n and concomitant partial arrest in the G(2)/M phase of the cell cycle. Fur ther analysis using a panel of cell lines, expressing H-2K(d), and transfec ted with the cDNA for various putative autoantigens in type 1 diabetes show ed that 4A7.7.15 recognizes insulin as an antigen. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.