Welters, Carlotta and Welters, Marthe-Lina and Stadler, Serena and Bullinger, Lars and Strobel, Julian and Hackstein, Holger and Dhamodaran, Arunraj and Blankenstein, Thomas and Hansmann, Leo (2024) HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation. HAEMATOLOGICA, 109 (4). pp. 1121-1127. ISSN 0390-6078, 1592-8721
Full text not available from this repository. (Request a copy)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-g 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TARGET ANTIGENS; HLA; HLA-CW-ASTERISK-0409N; ALLELES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2026 15:01 |
| Last Modified: | 26 Jan 2026 15:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64593 |
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