| Title |
The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA
|
|---|---|
| Published in |
Immunogenetics, November 2015
|
| DOI | 10.1007/s00251-015-0884-8 |
| Pubmed ID | |
| Authors |
Antje Isernhagen, Daniela Schilling, Sebastian Monecke, Pranali Shah, Leslie Elsner, Lutz Walter, Gabriele Multhoff, Ralf Dressel |
| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 48 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 29% |
| Researcher | 11 | 23% |
| Student > Master | 5 | 10% |
| Student > Bachelor | 4 | 8% |
| Student > Doctoral Student | 3 | 6% |
| Other | 5 | 10% |
| Unknown | 6 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 14 | 29% |
| Biochemistry, Genetics and Molecular Biology | 12 | 25% |
| Agricultural and Biological Sciences | 7 | 15% |
| Medicine and Dentistry | 4 | 8% |
| Computer Science | 1 | 2% |
| Other | 2 | 4% |
| Unknown | 8 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2015.
All research outputs
#18,345,259
of 23,577,654 outputs
Outputs from Immunogenetics
#1,017
of 1,213 outputs
Outputs of similar age
#266,226
of 389,834 outputs
Outputs of similar age from Immunogenetics
#11
of 15 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,213 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 389,834 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.