In:
European Journal of Immunology, Wiley, Vol. 50, No. 2 ( 2020-02), p. 270-283
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 gp100 209‐217 epitope, which is liberated from the melanoma differentiation antigen gp100 PMEL17 , 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 gp100 209‐217 ‐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.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201948116
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
1491907-2