Editing Proteasome (section)

==Role in the immune system==
The proteasome plays a straightforward but critical role in the function of the [[adaptive immunity|adaptive immune system]]. Peptide [[antigen]]s are displayed by the [[major histocompatibility complex]] class I (MHC) proteins on the surface of [[antigen-presenting cell]]s. These peptides are products of proteasomal degradation of proteins originated by the invading [[pathogen]]. Although constitutively expressed proteasomes can participate in this process, a specialized complex composed of proteins, whose [[gene expression|expression]] is induced by [[interferon gamma]], are the primary producers of peptides which are optimal in size and composition for MHC binding. These proteins whose expression increases during the immune response include the 11S regulatory particle, whose main known biological role is regulating the production of MHC ligands, and specialized β subunits called β1i, β2i, and β5i with altered substrate specificity. The complex formed with the specialized β subunits is known as the ''[[immunoproteasome]]''.<ref name="Wang" /> Another β5i variant subunit, β5t, is expressed in the thymus, leading to a thymus-specific "[[thymoproteasome]]" whose function is as yet unclear.<ref name="pmid17540904">{{cite journal | vauthors = Murata S, Sasaki K, Kishimoto T, Niwa S, Hayashi H, Takahama Y, Tanaka K | title = Regulation of CD8+ T cell development by thymus-specific proteasomes | journal = Science | volume = 316 | issue = 5829 | pages = 1349–53 | date = June 2007 | pmid = 17540904 | doi = 10.1126/science.1141915 | bibcode = 2007Sci...316.1349M | s2cid = 37185716 }}</ref>

The strength of MHC class I ligand binding is dependent on the composition of the ligand [[C-terminus]], as peptides bind by [[hydrogen bond]]ing and by close contacts with a region called the "B pocket" on the MHC surface. Many MHC class I alleles prefer hydrophobic C-terminal residues, and the immunoproteasome complex is more likely to generate hydrophobic C-termini.<ref name=Cascio2001>{{cite journal | vauthors = Cascio P, Hilton C, Kisselev AF, Rock KL, Goldberg AL | title = 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide | journal = The EMBO Journal | volume = 20 | issue = 10 | pages = 2357–66 | date = May 2001 | pmid = 11350924 | pmc = 125470 | doi = 10.1093/emboj/20.10.2357 }}</ref>

Due to its role in generating the activated form of [[NF-κB]], an anti-[[apoptosis|apoptotic]] and pro-[[Inflammation|inflammatory]] regulator of [[cytokine]] expression, proteasomal activity has been linked to inflammatory and [[autoimmune disease]]s. Increased levels of proteasome activity correlate with disease activity and have been implicated in autoimmune diseases including [[systemic lupus erythematosus]] and [[rheumatoid arthritis]].<ref name="Wang" />

The proteasome is also involved in [[Intracellular antibody-mediated proteolysis]] of antibody-bound virions. In this neutralisation pathway, [[TRIM21]] (a protein of the tripartite motif family) binds with [[immunoglobulin G]] to direct the virion to the proteasome where it is degraded.<ref name="pnas1014074107">{{cite journal | vauthors = Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC | title = Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 46 | pages = 19985–19990 | date = November 2010 | pmid = 21045130 | pmc = 2993423 | doi = 10.1073/pnas.1014074107 | bibcode = 2010PNAS..10719985M | doi-access = free }}</ref>