ArticleImmunogenetics2016
The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA.
Article in Immunogenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Review of Genetic Variation as a Predictive Biomarker for Chronic Graft-Versus-Host-Disease After Allogeneic Stem Cell Transplantation.Frontiers in immunology · 2020Pooled it
- Trial
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- Association Between Amino Acid Polymorphisms in MICA and MICA-NKG2D Interaction Affinity: Implications and Significance for Tumor Immunity.Biomolecules · 2025Review
- Impact of Esomeprazole, Ciprofloxacin and Their Combination on Cervical Cancer Cell Line Proliferation: A Focus on Heat Shock Protein 70 Modulation.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- A potential mechanism of tumor immune escape: Regulation and application of soluble natural killer group 2 member D ligands (Review).Oncology reports · 2024Review
- FunctionalInternational journal of molecular sciences · 2024Article
- Role of NKG2D ligands and receptor in haploidentical related donor hematopoietic cell transplantation.Blood advances · 2023Article
- Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT.Journal of clinical medicine · 2021Article
- Article
- Genetic variants in NKG2D axis and susceptibility to Epstein-Barr virus-induced nasopharyngeal carcinoma.Journal of cancer research and clinical oncology · 2021Article
- Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation.Frontiers in immunology · 2021Review
- Manipulating the NKG2D Receptor-Ligand Axis Using CRISPR: Novel Technologies for Improved Host Immunity.Frontiers in immunology · 2021Article
- MICA polymorphisms associated with antithyroid drug-induced agranulocytosis in the Chinese Han population.Immunity, inflammation and disease · 2020Article
- Association of MICA-129Met/Val polymorphism with clinical outcome of anti-TNF therapy and MICA serum levels in patients with rheumatoid arthritis.The pharmacogenomics journal · 2020Article
- NKG2D Ligand Shedding in Response to Stress: Role of ADAM10.Frontiers in immunology · 2020Review
- Cancer Exosomes as Conveyors of Stress-Induced Molecules: New Players in the Modulation of NK Cell Response.International journal of molecular sciences · 2019Review
- Post-translational Mechanisms Regulating NK Cell Activating Receptors and Their Ligands in Cancer: Potential Targets for Therapeutic Intervention.Frontiers in immunology · 2019Review
- NKG2D/NKG2-Ligand Pathway Offers New Opportunities in Cancer Treatment.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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