Thymoproteasome: probable role in generating positively selecting peptides

The proteasome is the protein destroying machinery conserved in all eukaryotes and plays essential roles in various cellular processes. Apart from the conserved ‘standard’ proteasome, a special type of proteasome called ‘immunoproteasome’ exists in vertebrates for better presentation of antigenic peptides on MHC class I molecules. Recently, another vertebrate-specific proteasome was discovered in the thymus. This ‘thymoproteasome’ has a novel catalytic subunit ‘β5t’ with unusual enzymatic activity and is expressed exclusively in cortical thymic epithelial cells (cTECs), which catalyze positive selection of developing thymocytes. β5t-deficient mice exhibit severe impairment in CD8+ T cell development. These findings suggest that cTECs are quite unique cells capable of presenting a unique set of self-peptides that are not seen in other cells and are required for positive selection of CD8+ T cells.