Thymoproteasome: role in thymic selection and clinical significance as a diagnostic marker for thymic epithelial tumors

Abstract

The thymoproteasome is a specialized type of proteasomes expressed exclusively in the thymic cortex. It has a unique catalytic subunit β5t with unusual enzymatic activity. The thymoproteasome exhibits lower chymotrypsin-like activity than other forms of proteasomes such as constitutive proteasomes and immunoproteasomes. Its cleavage specificity appears uniquely suited for the production of peptides that mediate positive selection of CD8⁺ T cells. Similar to major histocompatibility complex molecules and T/B-cell receptors, the thymoproteasome occurs only in jawed vertebrates, suggesting that it evolved concomitant with the cardinal elements of adaptive immunity. β5t can be used as a marker in the differential diagnosis of thymic tumors. It is expressed in most type B and some type AB thymomas, but not in type A thymoma, thymic carcinoma, or tumors of non-thymic epithelial origin.