title: An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope.
abstract: Most of the peptides presented by major histocompatibility complex (MHC) class I molecules require processing by proteasomes. Tripeptidyl peptidase II (TPPII), an aminopeptidase with endoproteolytic activity, may also have a role in antigen processing. Here, we analyzed the processing and presentation of the immunodominant human immunodeficiency virus epitope HIV-Nef(73-82) in human dendritic cells. We found that inhibition of proteasome activity did not impair Nef(73-82) epitope presentation. In contrast, specific inhibition of TPPII led to a reduction of Nef(73-82) epitope presentation. We propose that TPPII can act in combination with or independent of the proteasome system and can generate epitopes that evade generation by the proteasome-system.
authors.affiliation: Institut für Biochemie-Charité, Medical Faculty of the Humboldt-University Berlin, Monbijoustr. 2, 10117 Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Seifert
authors.forename: Concepción
authors.initials: C
authors.lastname: Marañón
authors.forename: Ayelet
authors.initials: A
authors.lastname: Shmueli
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Desoutter
authors.forename: Lisa
authors.initials: L
authors.lastname: Wesoloski
authors.forename: Katharina
authors.initials: K
authors.lastname: Janek
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Susanne
authors.initials: S
authors.lastname: Diescher
authors.forename: Muriel
authors.initials: M
authors.lastname: Andrieu
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
authors.forename: Toni
authors.initials: T
authors.lastname: Weinschenk
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Diego
authors.initials: D
authors.lastname: Laderach
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
authors.forename: Gaby
authors.initials: G
authors.lastname: Haas
authors.forename: Peter-M
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Yuval
authors.initials: Y
authors.lastname: Reiss
authors.forename: Anne
authors.initials: A
authors.lastname: Hosmalin
mesh_terms: D000626:Aminopeptidases; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000096:biosynthesis*; D006678:HIV / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009842:Oligopeptides; D034741:RNA, Small Interfering; D010450:Endopeptidases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C078846:epoxomicin