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The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation.

Isernhagen A, Malzahn D, Viktorova E, Elsner L, Monecke S, von Bonin F, Kilisch M, Wermuth JM, Walther N, Balavarca Y, Stahl-Hennig C, Engelke M, Walter L, Bickeböller H, Kube D, Wulf G, Dressel R - EMBO Mol Med (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.

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Degranulation of CD56dimCD16+ and CD56brightCD16+ NK cells in response to the MICA-129Met and the MICA-129Val isoformsPurified IL-2-stimulated NK cells (100 U/ml for 4 days) were cultured for 2 h on plates coated with MICA-129Met-Fc, MICA-129Val-Fc, or OVA-Fc proteins (10 μg/ml) before flow cytometry. The NK-cell populations were gated as illustrated in the upper panel (CD56dimCD16+, CD56brightCD16+, CD56brightCD16−), and CD107a expression was determined as displayed in the lower panel (red: CD107a, black: isotype control). The specific MFI (MFI CD107a minus MFI isotype control) and the percentage of CD107a+ cells are indicated.A summary (means + SD) of 5 experiments is shown. The data were analyzed by t-test, and the P-values of significant differences are indicated.
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fig10ev: Degranulation of CD56dimCD16+ and CD56brightCD16+ NK cells in response to the MICA-129Met and the MICA-129Val isoformsPurified IL-2-stimulated NK cells (100 U/ml for 4 days) were cultured for 2 h on plates coated with MICA-129Met-Fc, MICA-129Val-Fc, or OVA-Fc proteins (10 μg/ml) before flow cytometry. The NK-cell populations were gated as illustrated in the upper panel (CD56dimCD16+, CD56brightCD16+, CD56brightCD16−), and CD107a expression was determined as displayed in the lower panel (red: CD107a, black: isotype control). The specific MFI (MFI CD107a minus MFI isotype control) and the percentage of CD107a+ cells are indicated.A summary (means + SD) of 5 experiments is shown. The data were analyzed by t-test, and the P-values of significant differences are indicated.

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).


The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation.

Isernhagen A, Malzahn D, Viktorova E, Elsner L, Monecke S, von Bonin F, Kilisch M, Wermuth JM, Walther N, Balavarca Y, Stahl-Hennig C, Engelke M, Walter L, Bickeböller H, Kube D, Wulf G, Dressel R - EMBO Mol Med (2015)

Degranulation of CD56dimCD16+ and CD56brightCD16+ NK cells in response to the MICA-129Met and the MICA-129Val isoformsPurified IL-2-stimulated NK cells (100 U/ml for 4 days) were cultured for 2 h on plates coated with MICA-129Met-Fc, MICA-129Val-Fc, or OVA-Fc proteins (10 μg/ml) before flow cytometry. The NK-cell populations were gated as illustrated in the upper panel (CD56dimCD16+, CD56brightCD16+, CD56brightCD16−), and CD107a expression was determined as displayed in the lower panel (red: CD107a, black: isotype control). The specific MFI (MFI CD107a minus MFI isotype control) and the percentage of CD107a+ cells are indicated.A summary (means + SD) of 5 experiments is shown. The data were analyzed by t-test, and the P-values of significant differences are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644379&req=5

fig10ev: Degranulation of CD56dimCD16+ and CD56brightCD16+ NK cells in response to the MICA-129Met and the MICA-129Val isoformsPurified IL-2-stimulated NK cells (100 U/ml for 4 days) were cultured for 2 h on plates coated with MICA-129Met-Fc, MICA-129Val-Fc, or OVA-Fc proteins (10 μg/ml) before flow cytometry. The NK-cell populations were gated as illustrated in the upper panel (CD56dimCD16+, CD56brightCD16+, CD56brightCD16−), and CD107a expression was determined as displayed in the lower panel (red: CD107a, black: isotype control). The specific MFI (MFI CD107a minus MFI isotype control) and the percentage of CD107a+ cells are indicated.A summary (means + SD) of 5 experiments is shown. The data were analyzed by t-test, and the P-values of significant differences are indicated.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany.

Show MeSH
Related in: MedlinePlus