Autophagy creates a CTL epitope that mimics tumor-associated antigens.
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 leuke...
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2012-01-01
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doaj-b4c4f7010cad4f8eb922ce946a3d120d2020-11-24T21:34:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4712610.1371/journal.pone.0047126Autophagy creates a CTL epitope that mimics tumor-associated antigens.Ayako Demachi-OkamuraHiroki TorikaiYoshiki AkatsukaHiroyuki MiyoshiTamotsu YoshimoriKiyotaka KuzushimaThe 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.http://europepmc.org/articles/PMC3469533?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ayako Demachi-Okamura Hiroki Torikai Yoshiki Akatsuka Hiroyuki Miyoshi Tamotsu Yoshimori Kiyotaka Kuzushima |
spellingShingle |
Ayako Demachi-Okamura Hiroki Torikai Yoshiki Akatsuka Hiroyuki Miyoshi Tamotsu Yoshimori Kiyotaka Kuzushima Autophagy creates a CTL epitope that mimics tumor-associated antigens. PLoS ONE |
author_facet |
Ayako Demachi-Okamura Hiroki Torikai Yoshiki Akatsuka Hiroyuki Miyoshi Tamotsu Yoshimori Kiyotaka Kuzushima |
author_sort |
Ayako Demachi-Okamura |
title |
Autophagy creates a CTL epitope that mimics tumor-associated antigens. |
title_short |
Autophagy creates a CTL epitope that mimics tumor-associated antigens. |
title_full |
Autophagy creates a CTL epitope that mimics tumor-associated antigens. |
title_fullStr |
Autophagy creates a CTL epitope that mimics tumor-associated antigens. |
title_full_unstemmed |
Autophagy creates a CTL epitope that mimics tumor-associated antigens. |
title_sort |
autophagy creates a ctl epitope that mimics tumor-associated antigens. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3469533?pdf=render |
work_keys_str_mv |
AT ayakodemachiokamura autophagycreatesactlepitopethatmimicstumorassociatedantigens AT hirokitorikai autophagycreatesactlepitopethatmimicstumorassociatedantigens AT yoshikiakatsuka autophagycreatesactlepitopethatmimicstumorassociatedantigens AT hiroyukimiyoshi autophagycreatesactlepitopethatmimicstumorassociatedantigens AT tamotsuyoshimori autophagycreatesactlepitopethatmimicstumorassociatedantigens AT kiyotakakuzushima autophagycreatesactlepitopethatmimicstumorassociatedantigens |
_version_ |
1725948686161149952 |