An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides.
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.
Saric
Tomo
T
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Chang
Shih-Chung
SC
Hattori
Akira
A
York
Ian A
IA
Markant
Shirley
S
Rock
Kenneth L
KL
Tsujimoto
Masafumi
M
Goldberg
Alfred L
AL
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*
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011498:Protein Precursors; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase