MHC class I genes are subject to both homeostatic, tissue-specific regulation and dynamic regulation. Among the mechanisms of dynamic regulation are those mediated by hormones that either increase or decrease transcription of the genes. The observation that TSH leads to decreased class I transcription, whereas thyroid hormone leads to increased transcription, led to the hypothesis that failure to appropriately regulate MHC class I molecules may play a pivotal role in the generation of autoimmune disease. Consistent with this hypothesis, it was demonstrated that in an experimental model of autoimmunity, animals that fail to express class I molecules are resistant to disease.
