%0 Journal Article
%T Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens
%A Ayako Demachi-Okamura
%A Hiroki Torikai
%A Yoshiki Akatsuka
%A Hiroyuki Miyoshi
%A Tamotsu Yoshimori
%A Kiyotaka Kuzushima
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0047126
%X The detailed mechanisms responsible for processing tumor-associated antigens and presenting them to CTLs remain to be fully elucidated. In this study, we demonstrate a unique CTL epitope generated from the ubiquitous protein puromycin-sensitive aminopeptidase, which is presented via HLA-A24 on leukemic and pancreatic cancer cells but not on normal fibroblasts or EBV-transformed B lymphoblastoid cells. The generation of this epitope requires proteasomal digestion and transportation from the endoplasmic reticulum to the Golgi apparatus and is sensitive to chloroquine-induced inhibition of acidification inside the endosome/lysosome. Epitope liberation depends on constitutively active autophagy, as confirmed with immunocytochemistry for the autophagosome marker LC3 as well as RNA interference targeting two different autophagy-related genes. Therefore, ubiquitously expressed proteins may be sources of specific tumor-associated antigens when processed through a unique mechanism involving autophagy.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047126