Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens

Ayako Demachi-Okamura, Hiroki Torikai, Yoshiki Akatsuka, Hiroyuki Miyoshi, Tamotsu Yoshimori, Kiyotaka Kuzushima

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere47126
JournalPloS one
Volume7
Issue number10
DOIs
Publication statusPublished - 11-10-2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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