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: Next, we exposed NK cells to MICA-expressing L cells. After adjustment to MICA expression intensity on different clones, CD56brightCD16− NK cells co-cultured with L-MICA-129Val targets expressed less IFNγ compared to cells exposed to MICA-129Met clones. The MFI of IFNγ was on average 12.5 units lower (P = 0.0032, ANCOVA), and 7.5%-points less CD56brightCD16− NK cells were IFNγ positive (P = 0.0061, ANCOVA). For CD56brightCD16− NK cells encountering the MICA-129Val variant, the proportion of IFNγ+ cells and the MFI of IFNγ increased with MICA expression intensity (regression coefficients 0.14 and 0.09, respectively), whereas cells exposed to the MICA-129Met variant expressed less IFNγ when co-cultured with targets with higher MICA expression intensity (MFI, regression coefficient −1.11; Fig4A). The results obtained for CD56brightCD16+ and CD56dimCD16+ NK cells in these experiments are shown in the Appendix Fig S7.
Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.