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| Content Provider | Springer Nature Link |
|---|---|
| Author | Isernhagen, Antje Schilling, Daniela Monecke, Sebastian Shah, Pranali Elsner, Leslie Walter, Lutz Multhoff, Gabriele Dressel, Ralf |
| Copyright Year | 2015 |
| Abstract | The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A polymorphism causing a valine to methionine exchange at position 129 affects binding to NKG2D, cytotoxicity, interferon-γ release by NK cells and activation of CD8+ T cells. It is known that tumors can escape NKG2D-mediated immune surveillance by proteolytic shedding of MICA. Therefore, we investigated whether this polymorphism affects plasma membrane expression (pmMICA) and shedding of MICA. Expression of pmMICA was higher in a panel of tumor (n = 16, P = 0.0699) and melanoma cell lines (n = 13, P = 0.0429) carrying the MICA-129Val/Val genotype. MICA-129Val homozygous melanoma cell lines released more soluble MICA (sMICA) by shedding (P = 0.0015). MICA-129Met or MICA-129Val isoforms differing only in this amino acid were expressed in the MICA-negative melanoma cell line Malme, and clones with similar pmMICA expression intensity were selected. The MICA-129Met clones released more sMICA (P = 0.0006), and a higher proportion of the MICA-129Met than the MICA-129Val variant was retained in intracellular compartments (P = 0.0199). The MICA-129Met clones also expressed more MICA messenger RNA (P = 0.0047). The latter phenotype was also observed in mouse L cells transfected with the MICA expression constructs (P = 0.0212). In conclusion, the MICA-129Met/Val dimorphism affects the expression density of MICA on the plasma membrane. More of the MICA-129Met variants were retained intracellularly. If expressed at the cell surface, the MICA-129Met isoform was more susceptible to shedding. Both processes appear to limit the cell surface expression of MICA-129Met variants that have a high binding avidity to NKG2D. |
| Starting Page | 109 |
| Ending Page | 123 |
| Page Count | 15 |
| File Format | |
| ISSN | 00937711 |
| Journal | Immunogenetics |
| Volume Number | 68 |
| Issue Number | 2 |
| e-ISSN | 14321211 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2015-11-19 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Single nucleotide polymorphism Major histocompatibility complex (MHC) class I chain-related molecules A (MICA) Plasma membrane expression Proteolytic shedding Tumor cells Immunology Human Genetics Gene Function Cell Biology Allergology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Immunology |
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