Journal Article

DKFZ-2023-01959

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png HLA-C*04:09N is expressed at the cell surface and triggers peptide-specific T-cell activation.

Welters, C. ; Welters, M.-L. ; Stadler, S.DKFZ* ; Bullinger, L.DKFZ* ; Strobel, J. ; Hackstein, H. ; Dhamodaran, A. ; Blankenstein, T. ; Hansmann, L. A.DKFZ*

2024
Ferrata Storti Foundation Pavia

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.

Note: 2024 Apr 1;109(4):1121-1127

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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