Regulation of CD8+ T cell development by thymus-specific proteasomes

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta 5t. beta 5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta 5t into proteasomes in place of beta 5 or beta 5i selectively reduces this activity. We also found that beta 5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta 5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.