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@ARTICLE{Schmidt:186731,
author = {K. Schmidt and M. Leisegang$^*$ and P.-M. Kloetzel},
title = {{ERAP}2 supports {TCR} recognition of three immunotherapy
targeted tumor epitopes},
journal = {Molecular immunology},
volume = {154},
issn = {0161-5890},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2023-00083},
pages = {61 - 68},
year = {2023},
abstract = {The therapy of cancer by adoptive T cell transfer (ACT)
requires T cell receptors (TCRs) with optimal affinity for
HLA class I-bound peptides (pHLA-I). But not every patient
responds to ACT. Therefore, it is critical to understand the
individual factors influencing the recognition of HLA class
I-bound peptides (pHLA-I) by TCRs. Focusing on three
immunotherapy-targeted human HLA-A* 02:01-presented T cell
epitopes we investigated the contribution of the ER-resident
aminopeptidases ERAP1 and ERAP2 to TCR recognition of cancer
cells. We found that ERAP2 on its own, when expressed in
ERAP-deficient cells, elicited a strong CTL response towards
the Tyrosinase368–376 epitope. In vitro generated
TAP-dependent N-terminally extended epitope precursor
peptides were differently customized by ERAP1 and ERAP2 and
thus may serve as potential source for the
Tyrosinase368–376 epitope. ERAP2 also influenced
recognition of the gp100209–217 tumor epitope and enhanced
T cell recognition of the MART-126/27–35 epitope in the
absence of ERAP1 expression. Our results underline the
relevance of ERAP2 for tumor epitope presentation and TCR
recognition and may need to be considered when designing ACT
in the future.},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.molimm.2022.12.010},
url = {https://inrepo02.dkfz.de/record/186731},
}