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

Haematologica Ferrata Storti Foundation

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

Charité - Universitätsmedizin Berlin DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE 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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