The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues

Nat Immunol. 2002 Dec;3(12):1177-84. doi: 10.1038/ni860. Epub 2002 Nov 18.


Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an eight-residue ovalbumin epitope from precursors extended on the NH2 terminus that were generated either in the ER or cytosol. Purified ERAP1 also trimmed nearly half the nine-residue peptides tested. By destroying such nine-residue peptides in normal human cells, ERAP1 reduced the overall supply of antigenic peptides. However, after interferon-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation*
  • Cell Line
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Flow Cytometry
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Leucyl Aminopeptidase / chemistry
  • Leucyl Aminopeptidase / immunology*
  • Ligands
  • Molecular Sequence Data
  • Ovalbumin / immunology
  • Signal Transduction / immunology


  • Epitopes
  • Histocompatibility Antigens Class I
  • Ligands
  • Ovalbumin
  • Leucyl Aminopeptidase
  • puromycin-insensitive leucyl-specific aminopeptidase

Associated data

  • GENBANK/AF183569
  • GENBANK/BC031772