Immunoproteasom

The immunoproteasome is a specialized form of the proteasome that functions in protein degradation and antigen processing within cells of the immune system. It is formed in response to inflammatory cytokines, most notably interferon-gamma, and is also expressed in many non-immune cells during immune activation. In the 20S proteasome core, the standard catalytic subunits β1, β2, and β5 are replaced by alternative subunits: β1i (LMP2), β2i (MECL-1), and β5i (LMP7). This substitution changes the proteolytic preferences of the core, favoring cleavage after hydrophobic or basic residues and producing peptide fragments that are well suited for MHC class I presentation.

The primary role of the immunoproteasome is to generate antigenic peptides that can be transported by TAP into the endoplasmic reticulum, where they are loaded onto MHC class I molecules for display on the cell surface to CD8+ T cells. This process is central to cytotoxic T cell responses against virally infected or transformed cells. The immunoproteasome is abundant in professional antigen-presenting cells such as dendritic cells, macrophages, and B cells, and it can be induced in other cell types by cytokine signaling.

Clinical and research relevance includes its involvement in shaping immune responses and inflammation. Altered immunoproteasome activity has been linked to autoimmune and inflammatory diseases, and selective inhibitors targeting the immunoproteasome subunits (for example, β5i) are being explored as potential therapeutic tools in autoimmunity and cancer. The immunoproteasome is distinct from the constitutive proteasome and from the thymoproteasome, which contains a different catalytic subunit, β5t.