TY - JOUR
T1 - Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
AU - Kessler, Jan H.
AU - Khan, Selina
AU - Seifert, Ulrike
AU - Le Gall, Sylvie
AU - Chow, K. Martin
AU - Paschen, Annette
AU - Bres-Vloemans, Sandra A.
AU - De Ru, Arnoud
AU - Van Montfoort, Nadine
AU - Franken, Kees L.M.C.
AU - Benckhuijsen, Willemien E.
AU - Brooks, Jill M.
AU - Van Hall, Thorbald
AU - Ray, Kallol
AU - Mulder, Arend
AU - Doxiadis, Ilias I.N.
AU - Van Swieten, Paul F.
AU - Overkleeft, Hermen S.
AU - Prat, Annik
AU - Tomkinson, Birgitta
AU - Neefjes, Jacques
AU - Kloetzel, Peter M.
AU - Rodgers, David W.
AU - Hersh, Louis B.
AU - Drijfhout, Jan W.
AU - Van Veelen, Peter A.
AU - Ossendorp, Ferry
AU - Melief, Cornelis J.M.
N1 - Funding Information:
We thank T. Dannenberg and K. Textoris-Taube for technical assistance. Supported by the Dutch Cancer Society (UL 2005-3245) and Stichting Vanderes.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
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.
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U2 - 10.1038/ni.1974
DO - 10.1038/ni.1974
M3 - Article
C2 - 21151101
AN - SCOPUS:78650310807
SN - 1529-2908
VL - 12
SP - 45
EP - 53
JO - Nature Immunology
JF - Nature Immunology
IS - 1
ER -
