title: Placental leucine aminopeptidase efficiently generates mature antigenic peptides in vitro but in patterns distinct from endoplasmic reticulum aminopeptidase 1.
abstract: All three members of the oxytocinase subfamily of M1 aminopeptidases, endoplasmic reticulum aminopeptidase 1 (ERAP1), ERAP2, and placental leucine aminopeptidase (PLAP), also known as insulin-regulated aminopeptidase, have been implicated in the generation of MHC class I-presented peptides. ERAP1 and 2 trim peptides in the endoplasmic reticulum for direct presentation, whereas PLAP has been recently implicated in cross-presentation. The best characterized member of the family, ERAP1, has unique enzymatic properties that fit well with its role in Ag processing. ERAP1 can trim a large variety of long peptide sequences and efficiently accumulate mature antigenic epitopes of 8-9 aa long. In this study, we evaluate the ability of PLAP to process antigenic peptide precursors in vitro and compare it with ERAP1. We find that, similar to ERAP1, PLAP can trim a variety of long peptide sequences efficiently and, in most cases, accumulates appreciable amounts of correct length mature antigenic epitope. Again, similar to ERAP1, PLAP continued trimming some of the epitopes tested and accumulated smaller products effectively destroying the epitope. However, the intermediate accumulation properties of ERAP1 and PLAP are distinct and epitope dependent, suggesting that these two enzymes may impose different selective pressures on epitope generation. Overall, although PLAP has the necessary enzymatic properties to participate in generating or destroying MHC class I-presented peptides, its trimming behavior is distinct from that of ERAP1, something that supports a separate role for these two enzymes in Ag processing.
authors.affiliation: Protein Chemistry Laboratory, Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research "Demokritos," Athens 15310, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Georgiadou
authors.forename: Arron
authors.initials: A
authors.lastname: Hearn
authors.forename: Irini
authors.initials: I
authors.lastname: Evnouchidou
authors.forename: Angeliki
authors.initials: A
authors.lastname: Chroni
authors.forename: Leondios
authors.initials: L
authors.lastname: Leondiadis
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
authors.forename: Efstratios
authors.initials: E
authors.lastname: Stratikos
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D010122:Cystinyl Aminopeptidase / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D013379:Substrate Specificity / Q000276:immunology
chemical_list: D000941:Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D011257:Pregnancy Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; D000626:Aminopeptidases; C464841:ERAP1 protein, human; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase