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@ARTICLE{Welters:283180,
author = {C. Welters and M.-L. Welters and S. Stadler$^*$ and L.
Bullinger$^*$ and J. Strobel and H. Hackstein and A.
Dhamodaran and T. Blankenstein and L. A. Hansmann$^*$},
title = {{HLA}-{C}*04:09{N} is expressed at the cell surface and
triggers peptide-specific {T}-cell activation.},
journal = {Haematologica},
volume = {109},
number = {4},
issn = {0390-6078},
address = {Pavia},
publisher = {Ferrata Storti Foundation},
reportid = {DKFZ-2023-01959},
pages = {1121-1127},
year = {2024},
note = {2024 Apr 1;109(4):1121-1127},
abstract = {The null allele HLA-C*04:09N differs from HLA-C*04:01 in a
frameshift mutation within its cytoplasmic domain, resulting
in translation of 32 additional amino acids that are assumed
to prevent cell surface expression. However, we recently
identified a multiple myeloma-reactive T-cell receptor (TCR)
that appeared to recognize antigen presented on HLA-C*04:09N
and encouraged us to ask whether HLA-C*04:09N, albeit not
easily detectable at the cell surface, can present antigen
sufficient for T-cell activation. We generated two HLA-class
I-deficient cell lines, re-expressed HLA-C*04:09N, detected
HLA expression by flow cytometry, and tested for T-cell
activation using a cytomegalovirus peptide-specific
HLA-C*04:01-restricted TCR. In both cell lines, HLA-C*04:09N
expression was detectable at the cell surface and could be
enhanced by IFN-γ exposure. Recombinant HLA-C*04:09N
expression was sufficient for T-cell activation in vitro,
which could be blocked by an HLA-class I-specific antibody,
suggesting HLA-TCR interaction at the cell surface.
Peripheral blood mononuclear cells isolated from an
individual who physiologically expressed HLA-C*04:09N
triggered peptide-specific T-cell activation, confirming our
results with cells with natural HLA expression levels. In
conclusion, we present peptide-specific
HLA-C*04:09N-restricted T-cell activation and suggest
consideration of this allele in the appropriate clinical
context such as allogeneic stem cell transplantation, or in
the setting of cellular therapy.},
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},
pubmed = {pmid:37767552},
doi = {10.3324/haematol.2023.283812},
url = {https://inrepo02.dkfz.de/record/283180},
}