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Some early studies aimed at deciphering the mechanisms involved in immunological tolerance, and its breakdown in cases of autoimmune disease, were based on generating transgenic mice that constitutively expressed a viral protein in the -islet cells of the pancreas. These mice were crossed to transgenic mice expressing a T-cell receptor specific for MHC class I bound to a peptide of this viral protein. The double transgenic mice generated large numbers of CD8 T cells capable of recognizing this viral antigen on -islet cells, yet the mice never spontaneously developed type I diabetes, a disease in which -islet cells are destroyed by T cells. This lack of response most likely reflects:
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