T-CELLS ARE RESPONSIVE TO THE SIMIAN-VIRUS 40 LARGE TUMOR-ANTIGEN TRANSGENICALLY EXPRESSED IN PANCREATIC-ISLETS

The qualities of a peripheral Ag that determine whether T cells will b e tolerant of or responsive to it are poorly understood. To approach t his problem, we studied the T cell response in a line of transgenic mi ce selectively expressing an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is directed to islet beta-cells in Ri p1-Tag3 (RT3) mice by a hybrid insulin promoter-SV40-T construct. Ag i s first detected on these cells between 10 and 12 wk after birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR recogn izing SV40-T in the context of the class I MHC molecule, H-2K(k). T ce ll response in the resultant RT3 TCR-double transgenic mice was then a nalyzed. T cells are fully responsive to SV40-T in RT3/FCR-transgenic mice, and T cells infiltrate the islets of both RT3 and RT3/TCR-transg enic mice. This work demonstrates that T cells may remain responsive t o self-Ag expressed outside the thymus, and that this responsiveness m ay result in autoimmunity. The developmentally delayed expression or t he oncogenic nature of SV40-T in the RT3-transgenic mice may be import ant in determining this T cell response.