In the immune system, T cells respond to fragments of antigenic proteins presented at the cell surface by molecules encoded by genes of the major histocompatibility complex. This process is vital not only for recognition of antigens carried by pathogens and tumors but also in the selection of T cells as they develop in the thymus. A large multisubunit complex called the proteasome, which exists in a variety of forms containing different catalytic subunits, generates these peptides. Murata et al. (see the Perspective by Bevan) now identify a proteasome subunit, β5t, that was found exclusively in the thymic epithelial cells and directs positive selection of T cells. Indeed, mice lacking β5t showed significant disruption of T cell development.
S. Murata, K. Sasaki, T. Kishimoto, S.-i. Niwa, H. Hayashi, Y. Takahama, K. Tanaka, Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316, 1349-1353 (2007). [Abstract] [Full Text]