During their development in the thymus, self-reactive T cells are purged from the repertoire if they recognize one of the thousands of peripheral tissue antigens (PTAs) expressed by medullary thymic epithelial cells (mTECs). The transcription factor (TF) AIRE has been considered to be a key driver of PTA expression and therefore of self-tolerance. But a new study suggests this is not the whole story. Instead, lineage-defining TFs drive mTECs to assume a variety of distinct characters, masquerading as diverse peripheral cell types.

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