The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation.
Bottom Line: A single nucleotide polymorphism causes a valine to methionine exchange at position 129.Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon-γ release, and faster co-stimulation of CD8(+) T cells.The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8(+) T cells than the MICA-129Val isoform.
Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.Show MeSH
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Mentions: The MICA-129Met-Fc protein indeed elicited significantly more NK-cell degranulation than the MICA-129Val-Fc protein (Fig3A) based on the MFI of the degranulation marker CD107a (P = 0.0011) and the percentage of CD107a+ NK cells (P = 0.0003; two-way ANCOVA adjusted for MICA protein concentration). CD56dimCD16+ and, to a lesser extent, CD16brightCD16+ NK cells responded to NKG2D engagement by degranulation in contrast to CD56brightCD16− NK cells (Fig EV2A). The MICA-129Met-Fc variant elicited in both CD16+ NK-cell populations significantly more degranulation than the MICA-129Val-Fc protein as indicated by the proportion of CD107a+ cells (P = 0.0108 and P = 0.0240, t-test) and the MFI of CD107a (P = 0.0250 and P = 0.0049, t-test; FigEV2B).
Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.