LMP7PSMB8

LMP7, also known as β5i or PSMB8, is a catalytic subunit of the immunoproteasome. The gene PSMB8 encodes this subunit and is located on chromosome 6p21.3 within the MHC locus. In cells exposed to inflammatory cytokines such as interferon-γ, the constitutive 20S proteasome replaces the standard β5 subunit with the immunoproteasome subunit β5i (LMP7), together with β1i and β2i. The incorporation of LMP7 alters the proteolytic activity of the core particle, promoting chymotrypsin-like cleavage preferences and preferential generation of peptides with hydrophobic C-termini that are well-suited for binding to MHC class I molecules.

Biological role: The immunoproteasome is enriched in antigen-presenting cells and inflamed tissues, supporting antigen processing for presentation to CD8+ T cells and shaping the immune repertoire. LMP7 thus participates in adaptive immunity by influencing peptide generation.

Clinical significance: Mutations in PSMB8 can lead to autoinflammatory diseases, notably proteasome-associated autoinflammatory syndromes such as Nakajo-Nishimura syndrome, reflecting impaired immunoproteasome function. Some studies suggest altered expression of PSMB8 in various autoimmune or infectious contexts.

Research and therapeutics: Selective inhibitors of LMP7 have been explored as anti-inflammatory strategies and in cancer immunomodulation, though clinical outcomes remain under investigation. The gene and protein are widely studied in immunology, structure-function analyses, and antigen processing.