An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope.
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.
Seifert
Ulrike
U
Institut für Biochemie-Charité, Medical Faculty of the Humboldt-University Berlin, Monbijoustr. 2, 10117 Berlin, Germany.
Marañón
Concepción
C
Shmueli
Ayelet
A
Desoutter
Jean-François
JF
Wesoloski
Lisa
L
Janek
Katharina
K
Henklein
Peter
P
Diescher
Susanne
S
Andrieu
Muriel
M
de la Salle
Henri
H
Weinschenk
Toni
T
Schild
Hansjörg
H
Laderach
Diego
D
Galy
Anne
A
Haas
Gaby
G
Kloetzel
Peter-M
PM
Reiss
Yuval
Y
Hosmalin
Anne
A
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
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