TY  - JOUR
AU  - Welters, Carlotta
AU  - Welters, Marthe-Lina
AU  - Stadler, Serena
AU  - Bullinger, Lars
AU  - Strobel, Julian
AU  - Hackstein, Holger
AU  - Dhamodaran, Arunraj
AU  - Blankenstein, Thomas
AU  - Hansmann, Leo Alexander
TI  - HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation.
JO  - Haematologica
VL  - 109
IS  - 4
SN  - 0390-6078
CY  - Pavia
PB  - Ferrata Storti Foundation
M1  - DKFZ-2023-01959
SP  - 1121-1127
PY  - 2024
N1  - 2024 Apr 1;109(4):1121-1127
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37767552
DO  - DOI:10.3324/haematol.2023.283812
UR  - https://inrepo02.dkfz.de/record/283180
ER  -