English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

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

MPS-Authors
/persons/resource/persons243114

Henze,  S.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons208298

Liepe,  J.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)

3179157_Suppl.pdf
(Supplementary material), 855KB

Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0005-4548-D
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.