Immunoproteasomen

The immunoproteasome is a specialized form of the proteasome that is expressed in immune cells and is induced by inflammatory cytokines, particularly interferon-γ. It replaces the constitutive catalytic subunits of the 20S core particle with three alternative subunits—β1i (LMP2, encoded by PSMB9), β2i (MECL-1, PSMB10), and β5i (LMP7, PSMB8). This substitution alters the proteolytic selectivity of the core and changes the repertoire of peptides produced for major histocompatibility complex (MHC) class I presentation.

As a result of its altered cleavage preferences, the immunoproteasome tends to generate peptides with hydrophobic or basic C-termini that are more compatible with binding to MHC class I molecules. This enhances the efficiency of antigen presentation to CD8+ T cells and supports immune surveillance against intracellular pathogens and tumors. Induction of the immunoproteasome is a hallmark of inflammatory states and is most prominent in professional antigen-presenting cells, though it can be upregulated in other cell types under inflammatory conditions.

The immunoproteasome can operate in coordination with regulatory complexes such as PA28/11S or the 19S regulator, and it represents a dynamic component of the antigen-processing pathway. It is distinct from the thymoproteasome of the thymus, which uses a different catalytic subunit set and contributes to T cell selection.

Clinical relevance includes associations with autoimmune diseases, infection responses, and cancer immunology. Selective inhibitors targeting immunoproteasome subunits (notably LMP7) are active areas of research for modulating immune responses.