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- W4387114517 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." @default.
- W4387114517 created "2023-09-29" @default.
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- W4387114517 date "2023-09-28" @default.
- W4387114517 modified "2023-10-17" @default.
- W4387114517 title "HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation" @default.
- W4387114517 doi "https://doi.org/10.3324/haematol.2023.283812" @default.
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- W4387114517 hasPublicationYear "2023" @default.
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