The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues.
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.
York
Ian A
IA
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA. Ian.York@umassmed.edu
Chang
Shih-Chung
SC
Saric
Tomo
T
Keys
Jennifer A
JA
Favreau
Janice M
JM
Goldberg
Alfred L
AL
Rock
Kenneth L
KL
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010047:Ovalbumin; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase