title: Proteasome subtypes and regulators in the processing of antigenic peptides presented by class I molecules of the major histocompatibility complex.
abstract: The proteasome is responsible for the breakdown of cellular proteins. Proteins targeted for degradation are allowed inside the proteasome particle, where they are cleaved into small peptides and released in the cytosol to be degraded into amino acids. In vertebrates, some of these peptides escape degradation in the cytosol, are loaded onto class I molecules of the major histocompatibility complex (MHC) and displayed at the cell surface for scrutiny by the immune system. The proteasome therefore plays a key role for the immune system: it provides a continued sampling of intracellular proteins, so that CD8-positive T-lymphocytes can kill cells expressing viral or tumoral proteins. Consequently, the repertoire of peptides displayed by MHC class I molecules at the cell surface depends on proteasome activity, which may vary according to the presence of proteasome subtypes and regulators. Besides standard proteasomes, cells may contain immunoproteasomes, intermediate proteasomes and thymoproteasomes. Cells may also contain regulators of proteasome activity, such as the 19S, PA28 and PA200 regulators. Here, we review the effects of these proteasome subtypes and regulators on the production of antigenic peptides. We also discuss an unexpected function of the proteasome discovered through the study of antigenic peptides: its ability to splice peptides.
authors.affiliation: Ludwig Institute for Cancer Research, Brussels 1200, Belgium. nathalie.vigneron@bru.licr.org.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vigneron
authors.affiliation: Ludwig Institute for Cancer Research, Brussels 1200, Belgium. benoit.vandeneynde@bru.licr.org.
authors.forename: Benoît J
authors.initials: BJ
authors.lastname: Van den Eynde
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D009124:Muscle Proteins; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; C085047:PSME1 protein, human; C521188:PSME4 protein, human