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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Bibliographic Details
Published in:PloS one 2012-10, Vol.7 (10), p.e47126-e47126
Main Authors: Demachi-Okamura, Ayako, Torikai, Hiroki, Akatsuka, Yoshiki, Miyoshi, Hiroyuki, Yoshimori, Tamotsu, Kuzushima, Kiyotaka
Format: Article
Language:English
Subjects:
Acetylcysteine - analogs & derivatives
Acetylcysteine - pharmacology
Acidification
Aminopeptidase
Aminopeptidases - genetics
Aminopeptidases - metabolism
Antigen (tumor-associated)
Antigen presentation
Antigen processing
Antigens
Antigens, Neoplasm - immunology
Autophagy
Autophagy (Cytology)
Autophagy - genetics
Autophagy - immunology
Beta cells
Biology
Cell death
Cell Line, Tumor
Chloroquine
Cloning
Cytotoxicity
Endoplasmic reticulum
Epitopes
Epitopes - drug effects
Epitopes - genetics
Epitopes - immunology
Fibroblasts
Fibroblasts - immunology
Genes
Genetic aspects
Golgi apparatus
Health aspects
Histocompatibility antigen HLA
HLA-A24 Antigen - genetics
HLA-A24 Antigen - immunology
Humans
Immunocytochemistry
Immunology
Leukemia
Leukemia - immunology
Leukemia - pathology
Lymphocytes
Lymphocytes T
Medicine
Molecular Mimicry
Pancreatic cancer
Pancreatic Neoplasms - immunology
Pancreatic Neoplasms - pathology
Peptides
Phagocytosis
Proteasomes
Proteins
Puromycin
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Recombinant Proteins - metabolism
Ribonucleic acid
RNA
RNA Interference
RNA-mediated interference
T cell receptors
T-Lymphocytes, Cytotoxic - immunology
Tumorigenesis
Vacuoles - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0047126