PMID- 21151101
OWN - NLM
STAT- MEDLINE
DCOM- 20110509
LR  - 20211020
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Linking)
VI  - 12
IP  - 1
DP  - 2011 Jan
TI  - Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T 
      cell epitopes.
PG  - 45-53
LID - 10.1038/ni.1974 [doi]
AB  - Cytotoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I 
      molecules on the cell surface. The C terminus of these CTL epitopes is considered 
      to be produced by the proteasome. Here we demonstrate that the cytosolic 
      endopeptidases nardilysin and thimet oligopeptidase (TOP) complemented proteasome 
      activity. Nardilysin and TOP were required, either together or alone, for the 
      generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL 
      epitope from Epstein-Barr virus protein EBNA3C, and a clinically important 
      epitope from the melanoma protein MART-1. TOP functioned as C-terminal trimming 
      peptidase in antigen processing, and nardilysin contributed to both the 
      C-terminal and N-terminal generation of CTL epitopes. By broadening the antigenic 
      peptide repertoire, nardilysin and TOP strengthen the immune defense against 
      intracellular pathogens and cancer.
FAU - Kessler, Jan H
AU  - Kessler JH
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands. j.h.kessler@amc.uva.nl
FAU - Khan, Selina
AU  - Khan S
FAU - Seifert, Ulrike
AU  - Seifert U
FAU - Le Gall, Sylvie
AU  - Le Gall S
FAU - Chow, K Martin
AU  - Chow KM
FAU - Paschen, Annette
AU  - Paschen A
FAU - Bres-Vloemans, Sandra A
AU  - Bres-Vloemans SA
FAU - de Ru, Arnoud
AU  - de Ru A
FAU - van Montfoort, Nadine
AU  - van Montfoort N
FAU - Franken, Kees L M C
AU  - Franken KL
FAU - Benckhuijsen, Willemien E
AU  - Benckhuijsen WE
FAU - Brooks, Jill M
AU  - Brooks JM
FAU - van Hall, Thorbald
AU  - van Hall T
FAU - Ray, Kallol
AU  - Ray K
FAU - Mulder, Arend
AU  - Mulder A
FAU - Doxiadis, Ilias I N
AU  - Doxiadis II
FAU - van Swieten, Paul F
AU  - van Swieten PF
FAU - Overkleeft, Hermen S
AU  - Overkleeft HS
FAU - Prat, Annik
AU  - Prat A
FAU - Tomkinson, Birgitta
AU  - Tomkinson B
FAU - Neefjes, Jacques
AU  - Neefjes J
FAU - Kloetzel, Peter M
AU  - Kloetzel PM
FAU - Rodgers, David W
AU  - Rodgers DW
FAU - Hersh, Louis B
AU  - Hersh LB
FAU - Drijfhout, Jan W
AU  - Drijfhout JW
FAU - van Veelen, Peter A
AU  - van Veelen PA
FAU - Ossendorp, Ferry
AU  - Ossendorp F
FAU - Melief, Cornelis J M
AU  - Melief CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101212
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.15 (thimet oligopeptidase)
RN  - EC 3.4.24.61 (nardilysin)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Antigen Presentation/genetics
MH  - Antigens, Neoplasm/chemistry/immunology/*metabolism
MH  - Cytotoxicity, Immunologic/genetics
MH  - Epitopes, T-Lymphocyte/chemistry/immunology/*metabolism
MH  - HLA-A3 Antigen/metabolism
MH  - Humans
MH  - K562 Cells
MH  - Metalloendopeptidases/genetics/immunology/*metabolism
MH  - Peptide Fragments/chemistry/immunology/metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - RNA, Small Interfering/genetics
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism/pathology
MH  - Transgenes/genetics
EDAT- 2010/12/15 06:00
MHDA- 2011/05/10 06:00
CRDT- 2010/12/15 06:00
PHST- 2010/06/14 00:00 [received]
PHST- 2010/11/17 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/05/10 06:00 [medline]
AID - ni.1974 [pii]
AID - 10.1038/ni.1974 [doi]
PST - ppublish
SO  - Nat Immunol. 2011 Jan;12(1):45-53. doi: 10.1038/ni.1974. Epub 2010 Dec 12.