The 20S proteasome is composed of 28 subunits, arranged as a cylinder-shaped structure made of four stacked hetero-heptameric rings: 1-7, 1-7, 1-7, and 1-7. 1, 2, and 5 function the catalytic subunit for proteolysis. Murata and colleagues recently identified a new catalytic  subunit called 5t, which is only expressed in thymic cortical epithelial cells and dominantly incorporated into thymic 20S proteasomes. The integration of 5t into proteasomes reduces their chymotrypsin-like activity responsible for producing high affinity peptides for MHC class I. The depletion of 5t in mice resulted in defective development of CD8 single positive T cells in the thymus, indicating that 5t has a key role for generating the MHC class I-restricted CD8+T cell repertoire during thymic selection. There results challenge the 15 years old theory of T-cell development, particularly positive selection in the thymus and the phenomenon of peripheral tolerance.