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@ARTICLE{Aflalo:306260,
author = {A. Aflalo and A. F. Altenburg and M. Wacker and E. Khanfar
and J. Bauer$^*$ and J. S. Walz$^*$ and L. H. Boyle},
title = {{TAPBPR} promotes editing of the {HLA}-{B}44 peptide
repertoire, increasing the presentation of peptides
containing a {C}-terminal tryptophan.},
journal = {Frontiers in immunology},
volume = {16},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2025-02489},
pages = {1685705},
year = {2025},
abstract = {Major histocompatibility complex class I (MHC-I) molecules
play a key part in the adaptive immune response by
presenting antigens to CD8+ T cells. The high degree of
polymorphism in MHC-I leads to significant variation in
their dependence on the components of the antigen processing
and presentation pathway, such as the transporter associated
with antigen processing (TAP) and tapasin, and their
affinity for the peptide editor TAP-binding protein related
(TAPBPR). Here, we investigated the influence of TAPBPR on
the cell surface phenotype and peptide repertoire presented
by two human leukocyte antigen (HLA) class I allotypes,
HLA-B*44:02 and HLA-B*44:05, which are known to differ
drastically in their dependence on tapasin. TAPBPR bound
weakly to both HLA-B*44:02 and HLA-B*44:05. In contrast to
tapasin depletion, the loss of TAPBPR has a limited effect
on the cell surface expression of these two molecules.
Analysis of the immunopeptidomes presented in the presence
and absence of TAPBPR revealed that TAPBPR expression
restricted the peptide repertoire presented on HLA-B*44:05,
while it diversified the repertoire presented on
HLA-B*44:02. Overall, TAPBPR improved the predicted affinity
of the peptides displayed on both the HLA-B44 molecules.
Furthermore, TAPBPR enhanced the presentation of peptides
containing a C-terminal tryptophan residue. Our results show
that TAPBPR can significantly impact the peptide repertoire
of MHC-I molecules to which it binds weakly. Furthermore,
this represents the first study that points to a role for
TAPBPR in selecting a specific peptide sequence on MHC class
I molecules.},
keywords = {Humans / Antigen Presentation: immunology / HLA-B44
Antigen: immunology / HLA-B44 Antigen: metabolism / HLA-B44
Antigen: genetics / Tryptophan: immunology / Peptides:
immunology / Protein Binding / Membrane Transport Proteins /
CD8-Positive T-Lymphocytes: immunology / HLA (Other) / MHC
(Other) / TAPBPR (Other) / antigen presentation (Other) /
immunopeptidomics (Other) / HLA-B44 Antigen (NLM Chemicals)
/ Tryptophan (NLM Chemicals) / Peptides (NLM Chemicals) /
tapasin (NLM Chemicals) / Membrane Transport Proteins (NLM
Chemicals)},
cin = {TU01},
ddc = {610},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41246309},
pmc = {pmc:PMC12615179},
doi = {10.3389/fimmu.2025.1685705},
url = {https://inrepo02.dkfz.de/record/306260},
}