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  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. (2020). ER-aminopeptidase 1 determines the processing and presentation of an immunotherapy-relevant melanoma epitope. European Journal of Immunology, 50(2), 270-283. doi:10.1002/eji.201948116.

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 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              

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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.

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Language(s): eng - English
 Dates: 2019-11-272020-02-04
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/eji.201948116
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Title: European Journal of Immunology
Source Genre: Journal
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Pages: - Volume / Issue: 50 (2) Sequence Number: - Start / End Page: 270 - 283 Identifier: -