Thymoproteasomes

Thymoproteasomes are a specialized form of proteasome found predominantly in the thymic cortex of mammals. They form part of the antigen-processing machinery that generates peptides for presentation by MHC class I molecules. The defining feature of thymoproteasomes is the incorporation of a thymus-specific catalytic subunit, beta5t (PSMB11), in place of the standard beta5 subunit of the constitutive proteasome. The rest of the core particle shares the general architecture of the 20S proteasome.

Expression and localization: Thymoproteasomes are produced mainly by cortical thymic epithelial cells in the thymus; outside the thymus, their expression is minimal. Levels are highest during thymic development and decline with age as thymic function wanes.

Function and significance: The unique peptide repertoire generated by thymoproteasomes is presented by MHC class I on cortical thymic epithelial cells to developing thymocytes undergoing positive selection, particularly affecting CD8+ T cell development. Experimental disruption of beta5t impairs CD8+ T cell maturation, demonstrating a critical role in shaping the cytotoxic T cell repertoire and contributing to central tolerance.

Relation to broader immunity: Thymoproteasomes illustrate tissue-specific tailoring of antigen processing to developmental needs. Although best studied in mice, evidence suggests a conserved role in human thymic T cell development. Research continues to clarify how beta5t-dependent peptide generation influences TCR selection and immune competence, and how aging and disease may affect thymoproteasome function.