HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation.
Welters C, Welters ML, Stadler S, Bullinger L, Strobel J, Hackstein H, Dhamodaran A, Blankenstein T, Hansmann L (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 109
Pages Range: 1121-1127
Journal Issue: 4
DOI: 10.3324/haematol.2023.283812
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 HLAC* 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.
Authors with CRIS profile
Julian Strobel
Medizinische Fakultät
Holger Hackstein
Professur für Transfusionsmedizin und Cell-Engineering
Involved external institutions
Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
How to cite
APA:
Welters, C., Welters, M.L., Stadler, S., Bullinger, L., Strobel, J., Hackstein, H.,... Hansmann, L. (2024). HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation. Haematologica, 109(4), 1121-1127. https://doi.org/10.3324/haematol.2023.283812
MLA:
Welters, Carlotta, et al. "HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation." Haematologica 109.4 (2024): 1121-1127.
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