title: An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides.
abstract: Precursors to major histocompatibility complex (MHC) class I-presented peptides with extra NH2-terminal residues can be efficiently trimmed to mature epitopes in the endoplasmic reticulum (ER). Here, we purified from liver microsomes a lumenal, soluble aminopeptidase that removes NH2-terminal residues from many antigenic precursors. It was identified as a metallopeptidase named "adipocyte-derived leucine" or "puromycin-insensitive leucine-specific" aminopeptidase. However, because we localized it to the ER, we propose it be renamed ER-aminopeptidase 1 (ERAP1). ERAP1 is inhibited by agents that block precursor trimming in ER vesicles and although it trimmed NH2-extended precursors, it spared presented peptides of 8 amino acid and less. Like other proteins involved in antigen presentation, ERAP1 is induced by interferon-gamma. When overexpressed in vivo, we found that ERAP1 stimulates the processing and presentation of an antigenic precursor in the ER.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.forename: Shih-Chung
authors.initials: SC
authors.lastname: Chang
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
authors.forename: Shirley
authors.initials: S
authors.lastname: Markant
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001692:Biological Transport / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D007931:Leucyl Aminopeptidase / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011498:Protein Precursors; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase