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| Item Type: | Article |
|---|---|
| Title: | HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation |
| Creators Name: | Welters, C. and Welters, M.L. and Stadler, S. and Bullinger, L. and Strobel, J. and Hackstein, H. and Dhamodaran, A. and Blankenstein, T. and Hansmann, L. |
| 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 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. |
| Keywords: | Cytotoxic T-Lymphocytes, HLA-C Antigens, Mononuclear Leukocytes, Peptides, T-Cell Antigen Receptors |
| Source: | Haematologica |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Volume: | 109 |
| Number: | 4 |
| Page Range: | 1121-1127 |
| Date: | April 2024 |
| Official Publication: | https://doi.org/10.3324/haematol.2023.283812 |
| PubMed: | View item in PubMed |
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