immunoproteasome

The immunoproteasome is a specialized form of the proteasome that enhances the generation of peptide antigens for presentation by MHC class I molecules. It is formed in response to inflammatory cytokines, particularly interferon-γ, and differs from the constitutive proteasome by replacing three catalytic subunits with inducible counterparts: β1i (LMP2, encoded by PSMB9), β2i (MECL-1, PSMB10), and β5i (LMP7, PSMB8).

This subunit exchange alters proteolytic cleavage preferences, increasing production of peptides with C termini favored by MHC class I binding. As a result, the immunoproteasome enhances antigen processing and presentation to CD8+ T cells. It can associate with regulatory particles such as PA28 (11S) to further modulate peptide generation.

Expression is highest in professional antigen-presenting cells such as dendritic cells, B cells, and macrophages, and is upregulated in other cell types under inflammatory conditions. The immunoproteasome plays a central role in antiviral and antitumor immunity, influences the repertoire of presented peptides, and has been implicated in autoimmunity and cancer. Therapeutically, selective inhibitors targeting immunoproteasome subunits are being investigated for immune modulation.