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Autophagy creates a CTL epitope that mimics tumor-associated antigens.


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.

SUBMITTER: Demachi-Okamura A 

PROVIDER: S-EPMC3469533 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Autophagy creates a CTL epitope that mimics tumor-associated antigens.

Demachi-Okamura Ayako A   Torikai Hiroki H   Akatsuka Yoshiki Y   Miyoshi Hiroyuki H   Yoshimori Tamotsu T   Kuzushima Kiyotaka K  

PloS one 20121011 10


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 endop  ...[more]

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