These studies shed new light on the molecular pathways that regulate the effector programming of innate-like T cells, reveal a new key molecular target of HDAC7 in T cell development, and set forth a novel cellular model of tissue-specific autoimmunity, in which one genetic lesion mediates multiple defects in thymic selection, which then converge in the periphery to produce a unique, tissue-restricted pattern of disease. The gene discussed is HDAC7; the disease is Autoimmunity.