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

Fingerprint

autophagy
Autophagy
Neoplasm Antigens
epitopes
Tumors
Epitopes
antigens
Antigens
neoplasms
HLA-A24 Antigen
puromycin
chloroquine
pancreatic neoplasms
endosomes
aminopeptidases
Acidification
Endosomes
Chloroquine
lysosomes
immunocytochemistry

All Science Journal Classification (ASJC) codes

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

Cite this

Demachi-Okamura, A., Torikai, H., Akatsuka, Y., Miyoshi, H., Yoshimori, T., & Kuzushima, K. (2012). Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens. PloS one, 7(10), [e47126]. https://doi.org/10.1371/journal.pone.0047126
Demachi-Okamura, Ayako ; Torikai, Hiroki ; Akatsuka, Yoshiki ; Miyoshi, Hiroyuki ; Yoshimori, Tamotsu ; Kuzushima, Kiyotaka. / Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens. In: PloS one. 2012 ; Vol. 7, No. 10.
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Demachi-Okamura, A, Torikai, H, Akatsuka, Y, Miyoshi, H, Yoshimori, T & Kuzushima, K 2012, 'Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens', PloS one, vol. 7, no. 10, e47126. https://doi.org/10.1371/journal.pone.0047126

Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens. / Demachi-Okamura, Ayako; Torikai, Hiroki; Akatsuka, Yoshiki; Miyoshi, Hiroyuki; Yoshimori, Tamotsu; Kuzushima, Kiyotaka.

In: PloS one, Vol. 7, No. 10, e47126, 11.10.2012.

Research output: Contribution to journalArticle

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Demachi-Okamura A, Torikai H, Akatsuka Y, Miyoshi H, Yoshimori T, Kuzushima K. Autophagy Creates a CTL Epitope That Mimics Tumor-Associated Antigens. PloS one. 2012 Oct 11;7(10). e47126. https://doi.org/10.1371/journal.pone.0047126