Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes

作者：Kessler Jan H^*; Khan Selina; Seifert Ulrike; Le Gall Sylvie; Chow K Martin; Paschen Annette; Bres Vloemans Sandra A; de Ru Arnoud; van Montfoort Nadine; Franken Kees L M C; Benckhuijsen Willemien E; Brooks Jill M; van Hall Thorbald; Ray Kallol; Mulder Arend; Doxiadis Ilias I N; van Swieten Paul F; Overkleeft Hermen S; Prat Annik; Tomkinson Birgitta; Neefjes Jacques; Kloetzel Peter M; Rodgers David W; Hersh Louis B; Drijfhout Jan W; van Veelen Peter A

来源：Nature Immunology, 2011, 12(1): 45-U67.

DOI：10.1038/ni.1974

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.

• 出版日期2011-1