%0 Journal Article
%A Welters, Carlotta
%A Welters, Marthe-Lina
%A Stadler, Serena
%A Bullinger, Lars
%A Strobel, Julian
%A Hackstein, Holger
%A Dhamodaran, Arunraj
%A Blankenstein, Thomas
%A Hansmann, Leo Alexander
%T HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation.
%J Haematologica
%V 109
%N 4
%@ 0390-6078
%C Pavia
%I Ferrata Storti Foundation
%M DKFZ-2023-01959
%P 1121-1127
%D 2024
%Z 2024 Apr 1;109(4):1121-1127
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37767552
%R 10.3324/haematol.2023.283812
%U https://inrepo02.dkfz.de/record/283180