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
Related in: MedlinePlus
Mentions: Notably, the NKG2D expression was significantly reduced on all three NK-cell subpopulations 4 and 24 h after exposure to MICA-expressing targets (FigEV4A). After adjustment to MICA expression intensities, the NKG2D expression was on average 19.5 (P = 8.04 × 10−6, CD56dimCD16+), 16.2 (P = 2.26 × 10−8, CD56brightCD16+), or 15.8%-points (P = 1.02 × 10−4, CD56brightCD16−) lower on NK cells exposed to L-MICA-129Met than L-MICA-129Val clones (FigEV4B). Hence, the MICA-129Met variant induced a stronger down-regulation of NKG2D than the MICA-129Val variant. This counter-regulation appears to limit the initially stronger functional effects of the MICA-129Met variant on NKG2D signaling.
Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.