English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  ER-aminopeptidase 1 determines the processing and presentation of an immunotherapy-relevant melanoma epitope.

Textoris‐Taube, K., Cammann, C., Henklein, P., Topfstedt, E., Ebstein, F., Henze, S., et al. (2019). ER-aminopeptidase 1 determines the processing and presentation of an immunotherapy-relevant melanoma epitope. European Journal of Immunology, (in press). doi:10.1002/eji.201948116.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0005-4548-D Version Permalink: http://hdl.handle.net/21.11116/0000-0005-454C-9
Genre: Journal Article

Files

show Files
hide Files
:
3179157.pdf (Preprint), 2MB
 
File Permalink:
-
Name:
3179157.pdf
Description:
-
Visibility:
Restricted ( Max Planck Society (every institute); )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
3179157_Suppl.pdf (Supplementary material), 855KB
Name:
3179157_Suppl.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Textoris‐Taube, K., Author
Cammann, C., Author
Henklein, P., Author
Topfstedt, E., Author
Ebstein, F., Author
Henze, S.1, Author              
Liepe, J.1, Author              
Zhao, F., Author
Schadendorf, D., Author
Dahlmann, B., Author
Uckert, W., Author
Paschen, A., Author
Mishto, M., Author
Seifert, U., Author
Affiliations:
1Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_2466694              

Content

show
hide
Free keywords: CD8+ T cells; ER-aminopeptidase; Proteasome; gp100; melanoma
 Abstract: Dissecting the different steps of the processing and presentation of tumor-associated antigens is a key aspect of immunotherapies enabling to tackle the immune response evasion attempts of cancer cells. The immunodominant glycoprotein gp100209-217 epitope, which is liberated from the melanoma differentiation antigen gp100PMEL17 , is part of immunotherapy trials. By analyzing different human melanoma cell lines, we here demonstrate that a pool of N-terminal extended peptides sharing the common minimal epitope is generated by melanoma proteasome subtypes. In vitro and in cellulo experiments indicate that ER-resident aminopeptidase 1 (ERAP1) - but not ERAP2 - defines the processing of this peptide pool thereby modulating the T cell recognition of melanoma cells. By combining the outcomes of our studies and others, we can sketch the complex processing and endogenous presentation pathway of the gp100209-217 -containing epitope/peptides, which are produced by proteasomes and are translocated to the vesicular compartment through different pathways, where the precursor peptides that reach the endoplasmic reticulum are further processed by ERAP1. The latter step enhances the activation of epitope-specific T lymphocytes, which might be a target to improve the efficiency of anti-melanoma immunotherapy.

Details

show
hide
Language(s): eng - English
 Dates: 2019-11-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/eji.201948116
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: European Journal of Immunology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: - Sequence Number: (in press) Start / End Page: - Identifier: -