An IFN-gamma-induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I-presented peptides

Nat Immunol. 2002 Dec;3(12):1169-76. doi: 10.1038/ni859. Epub 2002 Nov 18.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Biological Transport / immunology
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / immunology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology*
  • Leucyl Aminopeptidase / chemistry
  • Leucyl Aminopeptidase / immunology*
  • Ligands
  • Mice
  • Microsomes, Liver / enzymology
  • Protein Precursors / chemistry
  • Protein Precursors / immunology
  • Signal Transduction / immunology*


  • Histocompatibility Antigens Class I
  • Ligands
  • Protein Precursors
  • Leucyl Aminopeptidase
  • puromycin-insensitive leucyl-specific aminopeptidase