Affinage

MICA

MHC class I polypeptide-related sequence A · UniProt Q29983

Length
383 aa
Mass
42.9 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICA is a stress-inducible cell-surface ligand for the activating immunoreceptor NKG2D that couples cellular stress states to NK-cell, γδ T-cell, and CD8+ T-cell cytotoxicity, functioning as a central node in immune surveillance of transformed, infected, and inflamed cells (PMID:15357948, PMID:29279329). Engagement of NKG2D by MICA drives degranulation, IFN-γ release, and target killing, with the natural MICA-129Met/Val dimorphism tuning the strength of this output: the Met variant binds NKG2D more strongly and elicits faster signaling but also drives more rapid NKG2D downregulation (PMID:26483398). Structurally, NKG2D binding involves a disordered-to-ordered transition of MICA, and mutations that destabilize the unbound state accelerate association and raise affinity (PMID:17690100). MICA expression is controlled at multiple levels: it is transcriptionally upregulated by NF-κB downstream of TNFα through a defined promoter element overlapping a heat-shock response element (PMID:22170063), by DNA-damage signaling through the ATM/ATR/CHK1 axis (PMID:18644891), by purine nucleotide metabolism and glycolysis (PMID:29279329), by T-cell activation and IL-2 signaling (PMID:11994503, PMID:16698439), and by estradiol in endometrial epithelium (PMID:18728002), while being repressed by HIF-1α under hypoxia (PMID:22992985), by miR-25-93-106b (PMID:24061441), and by the MUC1-C→NF-κB→EZH2/DNMT epigenetic axis (PMID:36754452). A dominant route of immune evasion is proteolytic shedding of the MICA ectodomain at its α3/stalk region by ADAM10 and ADAM17, generating soluble MICA that downregulates NKG2D; shedding requires the thiol oxidoreductase ERp5 and is governed by MUC1-C, which also controls exosomal MICA release via RAB27A (PMID:18676862, PMID:22215138, PMID:36754452, PMID:29873070). MICA additionally contributes to disease pathology, mediating intestinal epithelial cytotoxicity in celiac disease through IL-15-driven induction and NKG2D engagement (PMID:15357948). Antibodies targeting the α3 shedding site restore surface MICA and reactivate antitumor immunity through NK-cell NKG2D/CD16 effector functions and macrophage-mediated phagocytosis (PMID:29599246, PMID:34359073). Viral evasion is exemplified by HCMV UL147A, which arrests maturation of the prevalent MICA*008 allele and routes it for proteasomal degradation via its non-canonical GPI-anchoring pathway (PMID:33939764).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 Medium

    Established that MICA is not constitutively fixed but is induced as a marker of lymphocyte activation, defining it as a regulated stress/activation ligand rather than a static surface protein.

    Evidence Anti-CD3/CD28 stimulation of CD4+/CD8+ T cells with Western blot, RT-PCR, and flow cytometry

    PMID:11994503

    Open questions at the time
    • Does not define the transcription factors linking TCR signaling to the MICA promoter
    • Surface versus intracellular distribution of induced MICA not resolved
  2. 2004 High

    Demonstrated that MICA/NKG2D engagement directly drives tissue pathology, linking MICA induction to intestinal epithelial destruction in celiac disease.

    Evidence Gliadin challenge of intestinal epithelium, IL-15 dependence, anti-MICA/NKG2D blocking, coculture cytotoxicity, patient biopsies

    PMID:15357948

    Open questions at the time
    • Transcriptional mechanism of IL-15-driven MICA induction not detailed
    • Does not address shedding or soluble MICA in this context
  3. 2005 Medium

    Revealed two routes by which MICA suppresses immunity beyond direct activation: exosome-borne MICA downregulates effector NKG2D, and a distinct NKG2D-independent, IL-10-dependent pathway suppresses T-cell proliferation.

    Evidence Tumor exosome incubation with PBL plus antibody blocking; MICA stimulator cells with NKG2D blocking and IL-10 neutralization

    PMID:15885603 PMID:16091471

    Open questions at the time
    • Identity of the non-NKG2D MICA receptor unknown
    • Mechanism of MICA loading onto exosomes not defined
  4. 2006 Medium

    Showed MICA can act as an immunogen engaging adaptive responses through MHC class I/II independent of NKG2D, and that activated CD4+ T cells sequester MICA intracellularly to evade NK killing.

    Evidence rMICA immunization with proliferation/cytotoxicity assays and MHC/NKG2D blocking; confocal microscopy of intracellular MICA with NK cytotoxicity

    PMID:16698439 PMID:16698445

    Open questions at the time
    • Mechanism of intracellular retention not defined
    • Adaptive MICA antigen presentation pathway not molecularly mapped
  5. 2007 High

    Defined the biophysical basis of MICA-NKG2D recognition, showing the unbound MICA surface is disordered and that the association step is rate-limiting via a disorder-to-order transition.

    Evidence RosettaDesign mutagenesis of 15+ mutants with SPR kinetics and thermodynamics

    PMID:17690100

    Open questions at the time
    • In vitro biophysics only; cellular relevance of designed mutants untested
    • Does not address allelic affinity differences in physiological context
  6. 2008 High

    Identified ADAM10 and ADAM17 as the proteases that shed MICA at its stalk, establishing the molecular machinery of soluble MICA generation and tumor immune evasion.

    Evidence Reciprocal siRNA knockdown of ADAM10/ADAM17, inhibitor assays, stalk deletion mapping, soluble MICA ELISA

    PMID:18676862

    Open questions at the time
    • Does not define what triggers protease engagement of MICA
    • Relative contribution of each ADAM across tissues unresolved
  7. 2008 High

    Connected MICA induction to genome-instability sensing and to hormonal control, showing DNA damage signaling (ATM/ATR/CHK1) and estrogen-receptor signaling each upregulate MICA.

    Evidence Dicer knockdown with ATM/ATR/CHK1 inhibition and epistasis; estradiol treatment of uterine epithelium with ER antagonist and immunohistochemistry

    PMID:18644891 PMID:18728002

    Open questions at the time
    • Transcription factors executing DNA-damage-driven MICA induction not identified
    • Estrogen-responsive promoter elements not mapped
  8. 2011 High

    Mapped a defined NF-κB control site at -130 bp mediating TNFα-driven MICA transcription and showed it integrates with heat-shock signaling, providing a transcriptional mechanism for inflammatory MICA induction.

    Evidence Promoter reporter assays, site-directed mutagenesis, ChIP, dominant-negative HSF1 in primary endothelial cells, atherosclerotic lesion immunohistochemistry

    PMID:22170063

    Open questions at the time
    • Does not address how this site interacts with other inducers (DNA damage, metabolism)
    • Cell-type generality of the -130 element beyond endothelium not tested
  9. 2012 Medium

    Established additional shedding and repression mechanisms: ERp5/GRP78 surface translocation enables MICA shedding on CLL cells, and HIF-1α suppresses surface MICA under hypoxia.

    Evidence Co-localization and ERp5 pharmacological inhibition with soluble MICA ELISA; hypoxia culture with HIF-1α siRNA and surface/soluble MICA readouts

    PMID:22215138 PMID:22992985

    Open questions at the time
    • Mechanism linking ERp5 redox activity to ADAM cleavage not defined
    • HIF-1α acts transcriptionally or post-transcriptionally on MICA not resolved
  10. 2013 Medium

    Showed allele- and regulator-specific control of MICA fate, with the MICA*008 A5.1 frameshift diverting release to exosomes and the miR-25-93-106b cluster post-transcriptionally suppressing MICA.

    Evidence Comparative A5.1 vs wild-type endothelial expression with NK assays; bidirectional miRNA manipulation in HCC with NKG2D-binding and in vivo killing

    PMID:23539759 PMID:24061441

    Open questions at the time
    • Determinants channeling A5.1 MICA to exosomes versus protease cleavage not defined
    • Direct miRNA-MICA mRNA binding sites not mapped
  11. 2013 Medium

    Integrated endothelial MICA regulation, showing TNFα upregulates MICA via NF-κB/MAPK while IFNγ lowers it, with glycosylation and metalloproteinase activity as dominant post-transcriptional controls.

    Evidence Cytokine treatment of endothelial cells with NF-κB/MAPK, metalloproteinase, and glycosylation inhibitors; surface and soluble MICA readouts

    PMID:23860405

    Open questions at the time
    • Specific MAPK targets on the MICA promoter not identified
    • Glycosylation sites controlling MICA stability not mapped
  12. 2014 Medium

    Distinguished MICA from other NKG2D ligands mechanistically, showing MICA uniquely recruits the ubiquitin pathway and c-Cbl to drive NKG2D internalization and degradation.

    Evidence MICA vs ULBP2 NK stimulation, c-Cbl siRNA, ubiquitin pathway inhibitors, NKG2D internalization flow cytometry, cytotoxicity

    PMID:24846123

    Open questions at the time
    • Direct c-Cbl substrate ubiquitination of NKG2D not biochemically demonstrated
    • Why MICA but not ULBP2 engages c-Cbl is unexplained
  13. 2015 High

    Defined the functional consequences of the MICA-129Met/Val dimorphism, linking the Met variant's stronger NKG2D binding to faster signaling but greater NKG2D downregulation, intracellular retention, and shedding.

    Evidence NK cytotoxicity/IFN-γ assays, NKG2D flow cytometry, HSCT cohort (n=452); isogenic Met/Val transfectants with surface/soluble/intracellular MICA readouts

    PMID:26483398 PMID:26585323

    Open questions at the time
    • Structural basis of Met-driven intracellular retention not defined
    • Interaction of dimorphism with allele-specific shedding routes unresolved
  14. 2017 Medium

    Linked metabolic state to immune visibility, showing glycolysis and purine nucleotide synthesis are necessary and sufficient to induce MICA and enhance NKG2D-dependent killing.

    Evidence Metabolic inhibitors, metabolomics, surface MICA flow cytometry, NK cytotoxicity

    PMID:29279329

    Open questions at the time
    • Signaling that couples purine levels to MICA transcription not identified
    • Whether metabolic induction is transcriptional or post-transcriptional unresolved
  15. 2018 High

    Provided proof-of-concept that blocking MICA shedding at the α3 domain restores immune surveillance, and confirmed ADAM17 as the dominant sheddase in hepatocellular carcinoma with a druggable inhibitor.

    Evidence Rational α3-domain antibody with in vitro shedding inhibition and multiple in vivo tumor models plus NK depletion; ADAM17 siRNA and lomofungin enzymatic inhibition with knockdown-abolished rescue

    PMID:29599246 PMID:29873070

    Open questions at the time
    • Tissue-specific dominance of ADAM17 vs ADAM10 not generalized
    • Long-term resistance to shedding blockade not addressed
  16. 2021 High

    Defined an allele-specific viral evasion mechanism in which HCMV UL147A exploits the non-canonical GPI-anchoring pathway of MICA*008 to arrest its maturation and trigger proteasomal degradation.

    Evidence HCMV infection across MICA alleles, UL147A constructs, surface MICA flow cytometry, proteasome inhibitor rescue, GPI pathway dependence analysis

    PMID:33939764

    Open questions at the time
    • Molecular interface between UL147A and immature MICA*008 not resolved
    • Generalization to other MICA alleles using canonical anchoring not addressed
  17. 2022 High

    Expanded the effector mechanism of MICA-targeting therapy, showing α3-domain antibody 7C6 acts primarily through macrophage antibody-dependent phagocytosis and synergizes with HDAC inhibition to raise MICA/B.

    Evidence Macrophage depletion in AML models, ADCP assays, romidepsin-induced MICA/B expression, humanized AML model, primary patient cells

    PMID:34359073

    Open questions at the time
    • Relative contribution of macrophage versus NK effector arms across tumor types unresolved
    • Mechanism of romidepsin-driven MICA/B upregulation not molecularly defined
  18. 2023 High

    Unified transcriptional repression, shedding, and exosomal secretion under a single oncogenic regulator, showing MUC1-C represses MICA/B via NF-κB/EZH2/DNMT methylation while controlling ERp5-dependent shedding and RAB27A-dependent exosomal release.

    Evidence MUC1-C genetic/pharmacological targeting, ChIP for H3K27me3 and DNA methylation, Co-IP and direct binding for MUC1-C/ERp5 and MUC1-C/RAB27A, soluble/exosomal MICA assays, NK cytotoxicity

    PMID:36754452

    Open questions at the time
    • Direct recruitment of EZH2/DNMT to the MICA/B promoter by MUC1-C not structurally resolved
    • Hierarchy among the three MUC1-C-controlled mechanisms in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the non-NKG2D MICA receptor mediating IL-10-dependent T-cell suppression and the molecular determinants that select between protease shedding versus exosomal release remain unresolved.
  • No molecular identification of the NKG2D-independent MICA receptor
  • Switch governing exosomal versus enzymatic MICA release not defined
  • Integration of the many transcriptional inducers/repressors at the MICA locus not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ADAM10ADAM17C-CBLERP5GRP78MUC1-CNKG2DRAB27A

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MICA ectodomain shedding by tumor cells is mediated by ADAM10 and ADAM17 metalloproteases; silencing of ADAM10 or ADAM17 inhibited proteolytic release of soluble MICA from tumor cells, and the cleavage site maps to the stalk of the MICA ectodomain where deletions (but not alanine substitutions) impede shedding. siRNA knockdown of ADAM10/ADAM17 in tumor cell lines, small-molecule inhibitor/stimulator assays, ELISA for soluble MICA Cancer research High 18676862
2018 Antibodies targeting the MICA α3 domain (the site of proteolytic shedding) prevent loss of cell-surface MICA and MICB by human cancer cells and restore NKG2D-mediated NK cell immune surveillance; antitumor immunity was mediated mainly by NK cells through NKG2D and CD16 Fc receptors. Rational antibody design targeting α3 domain, in vitro shedding assays, multiple immunocompetent mouse tumor models, humanized mouse melanoma metastasis model, NK cell depletion experiments Science (New York, N.Y.) High 29599246
2004 MICA/NKG2D interaction directly mediates IEL cytotoxicity toward intestinal epithelial cells in celiac disease; gliadin (or its p31-49 peptide) induces MICA expression on gut epithelium via IL-15, which then triggers innate-like cytotoxicity and costimulates CD8 T cells through NKG2D engagement. In vitro gliadin challenge of intestinal epithelial cells, anti-MICA/NKG2D blocking antibodies, coculture cytotoxicity assays, patient biopsy analysis Immunity High 15357948
2015 The MICA-129Met isoform (strong NKG2D binder) elicits stronger NKG2D signaling, more NK-cell degranulation and IFN-γ release, and faster CD8+ T-cell costimulation than MICA-129Val; MICA-129Met also induces faster and stronger NKG2D downregulation on NK and CD8+ T cells, limiting surface NKG2D levels. Functional NK cytotoxicity assays, IFN-γ ELISA, flow cytometry for NKG2D surface expression, clinical HSCT cohort (n=452) EMBO molecular medicine High 26483398
2015 The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding: MICA-129Met variants are retained more in intracellular compartments, and when expressed at the cell surface are more susceptible to proteolytic shedding, resulting in lower net surface MICA-129Met density despite higher mRNA levels. Flow cytometry for surface MICA on panel of tumor/melanoma cell lines, ELISA for soluble MICA, transfection of MICA-129Met and -Val constructs into MICA-negative melanoma cells, intracellular MICA staining Immunogenetics Medium 26585323
2011 NF-κB regulates MICA transcription in endothelial cells via a defined control site at −130 bp upstream of the MICA transcription start site; TNFα-induced MICA upregulation is mediated through this NF-κB site, which overlaps with a heat shock response element integrating both pathways; lentiviral expression of a dominant-negative truncated HSF1 blocked the TNFα-driven MICA response. Reporter gene assays, site-directed mutagenesis of MICA promoter, ChIP, lentivirus-mediated gene delivery with dominant-negative HSF1 in primary human endothelial cells, immunohistochemistry of atherosclerotic lesions The Journal of biological chemistry High 22170063
2008 Decreased Dicer expression in human cells upregulates MICA and MICB via activation of the DNA damage response; MICA/B upregulation induced by Dicer knockdown was prevented by pharmacological or genetic inhibition of ATM, ATR, or CHK1, placing MICA/B induction downstream of DNA damage signaling. RNAi knockdown of Dicer, pharmacological inhibitors of ATM/ATR/CHK1, genetic epistasis with checkpoint kinase mutants, Western blot and flow cytometry for MICA/B The Journal of cell biology High 18644891
2014 MICA-induced NKG2D downregulation on human NK cells is mechanistically distinct from ULBP2-induced downregulation: MICA (but not ULBP2) engages the ubiquitin pathway and the E3 ligase c-Cbl to drive NKG2D internalization and lysosomal/proteasomal degradation. Comparison of MICA vs. ULBP2 stimulation of NK cells, c-Cbl siRNA knockdown, ubiquitin pathway inhibitors, flow cytometry for NKG2D surface expression and internalization, cytotoxicity assays European journal of immunology Medium 24846123
2007 Mutations designed to destabilize the unbound (disordered) region of MICA—rather than to stabilize the receptor-bound conformation—increased the NKG2D association rate and binding affinity by 0.9–1.8 kcal/mol; kinetic changes were primarily observed during association, consistent with the disordered-to-ordered conformational transition upon receptor binding. RosettaDesign computational mutagenesis, recombinant protein expression, surface plasmon resonance (SPR) kinetics and thermodynamics The Journal of biological chemistry High 17690100
2002 MICA expression on T lymphocytes is induced by T cell activation signals: engagement of CD3 or CD28 (with PMA) upregulates MICA protein and mRNA in both CD4+ and CD8+ T cells, as detected by Western blot, RT-PCR, and flow cytometry; activation reaches plateau at day 3–4. Anti-CD3 and anti-CD28 antibody stimulation, Western blot, RT-PCR, flow cytometry for surface MICA Journal of leukocyte biology Medium 11994503
2006 Activated CD4+ T lymphocytes retain MICA predominantly in intracellular compartments (visualized by confocal microscopy), resulting in low surface MICA expression; this intracellular retention appeared to protect activated CD4+ T cells from NKG2D-mediated NK cell killing, as MICA contribution to NK cytotoxicity was marginal despite inducible MICA protein expression. Confocal microscopy for intracellular MICA localization, NK cytotoxicity assays with anti-MICA blocking, Western blot, flow cytometry Human immunology Medium 16698439
2012 ERp5 (a thiol oxidoreductase) and GRP78, when translocated to the cell surface on chronic lymphocytic leukemia (CLL) cells, co-localize with MICA and are involved in proteolytic MICA shedding; pharmacological inhibition of ERp5 activity reduced soluble MICA release from CLL cells. Immunofluorescence and flow cytometry co-localization, correlation analysis, pharmacological ERp5 inhibition, ELISA for soluble MICA Cancer immunology, immunotherapy : CII Medium 22215138
2005 Tumor-derived exosomes bearing MICA (and other NKG2D ligands) reduce the proportion of NKG2D-expressing CD8+ T cells and CD3− effector cells and impair NKG2D-dependent cytotoxicity; blocking NKG2D ligands on exosomes with antibodies reversed this inhibition, establishing that exosomal MICA mediates immune evasion. Incubation of PBL with tumor exosomes, flow cytometry for NKG2D surface expression, anti-NKG2D ligand antibody blocking, in vitro cytotoxicity assays Blood cells, molecules & diseases Medium 15885603
2012 Hypoxia downregulates cell-surface MICA on osteosarcoma cells in a HIF-1α-dependent manner without increasing soluble MICA; siRNA knockdown of HIF-1α under hypoxia restored surface MICA expression and concomitantly increased soluble MICA, placing HIF-1α upstream of MICA suppression. Hypoxia chamber culture (1% O2), siRNA knockdown of HIF-1α, flow cytometry for surface MICA, ELISA for soluble MICA, NK cytotoxicity assay International journal of oncology Medium 22992985
2013 The MICA*008 A5.1 frameshift allele causes 7–10-fold higher MICA mRNA and surface protein expression on endothelial cells and shifts MICA release exclusively to exosomes rather than enzymatic (metalloproteinase) cleavage; A5.1 endothelial cells elicit enhanced NKG2D interaction and NK-cell-mediated lysis. Comparative expression analysis of A5.1 vs. wild-type EC, RT-PCR, Western blot, flow cytometry, NKG2D binding assay, NK cytotoxicity assay, exosome isolation Journal of the American Society of Nephrology : JASN Medium 23539759
2017 MICA expression is regulated by purine nucleotide metabolism: active glycolysis and purine synthesis are necessary to upregulate MICA, and increases in purine nucleotide levels alone are sufficient to induce MICA expression, with metabolic induction of MICA directly increasing NKG2D-dependent cytotoxicity. Metabolic interventions (glucose deprivation, glycolysis inhibitors, purine synthesis inhibitors), metabolomic analyses, flow cytometry for surface MICA, NK cytotoxicity assays The Journal of biological chemistry Medium 29279329
2005 MICA can mediate NKG2D-independent suppression of T cell proliferation; this suppressive effect requires IL-10 and involves a receptor other than NKG2D. T cell proliferation assays with MICA-expressing stimulator cells, NKG2D blocking antibodies, IL-10 neutralization/addition, genetic NKG2D-deficient cells Proceedings of the National Academy of Sciences of the United States of America Medium 16091471
2008 Estradiol upregulates MICA expression on uterine epithelial cells in an estrogen receptor-dependent manner; MICA protein was detected primarily on endometrial epithelial cells with greater expression in the secretory phase of the menstrual cycle. Estradiol treatment of uterine epithelial cells, estrogen receptor antagonist blocking, real-time PCR, immunohistochemistry of endometrial biopsies Clinical immunology (Orlando, Fla.) Medium 18728002
2021 The HCMV protein UL147A specifically downregulates the most prevalent MICA allele, MICA*008, by inducing its maturation arrest and additionally targeting it for proteasomal degradation; UL147A specificity for MICA*008 is determined by the non-canonical GPI anchoring pathway used by immature MICA*008. HCMV infection of cells expressing MICA*008 vs. other alleles, UL147A expression constructs, flow cytometry for surface MICA, proteasome inhibitor assays, mechanistic analysis of GPI pathway dependence PLoS pathogens High 33939764
2022 The MICA/B antibody 7C6 (targeting the α3 domain to inhibit shedding) promotes macrophage-mediated antibody-dependent phagocytosis of AML cells as the primary mechanism of antitumor efficacy; romidepsin (HDAC inhibitor) increased MICA/B surface expression and synergized with 7C6 to enhance macrophage phagocytosis and reduce leukemia burden. Macrophage depletion in mouse AML models, antibody-dependent phagocytosis assays, MICA/B expression by flow cytometry following romidepsin treatment, humanized AML mouse model, primary patient AML cells Blood High 34359073
2023 MUC1-C represses MICA and MICB expression through NF-κB-driven EZH2-mediated and DNMT-mediated methylation of the MICA/B promoter regions; MUC1-C also regulates ERp5 (required for MICA/B protease digestion and shedding) and interacts with RAB27A (required for exosome formation), thereby controlling both shedding and exosomal MICA/B secretion. Genetic and pharmacological MUC1-C targeting (GO-203 inhibitor), co-immunoprecipitation for MUC1-C/ERp5 and MUC1-C/RAB27A interactions, direct binding studies, ChIP for H3K27me3 and DNA methylation at MICA/B promoters, ELISA for shed MICA/B, exosome isolation and characterization, NK cytotoxicity assays Journal for immunotherapy of cancer High 36754452
2018 ADAM17 is the primary MICA sheddase in hepatocellular carcinoma cells; ADAM17 siRNA knockdown reduced soluble MICA levels and increased membrane-bound MICA; lomofungin enzymatically inhibits ADAM17 and dose-dependently restores membrane MICA while reducing soluble MICA shedding, with effects abolished by ADAM17 knockdown. siRNA knockdown of ADAM family members, ELISA for soluble MICA, flow cytometry for membrane MICA, in vitro ADAM17 enzymatic inhibition assay with FDA-approved drug library, structure-activity analysis of lomofungin analogs International journal of cancer High 29873070
2013 MicroRNAs of the miR-25-93-106b cluster suppress MICA expression in HCC cells; overexpression of this miRNA cluster significantly reduced MICA protein levels, while silencing enhanced MICA expression, with biologically significant effects on NKG2D binding and in vivo NK cell killing. miRNA overexpression and inhibition in HCC cells, Western blot for MICA, NKG2D-binding assay, in vivo cell-killing model Scientific reports Medium 24061441
2006 MICA antigens stimulate T cell proliferation and CD8+ T cell-mediated cytotoxicity in a manner dependent on MHC class I and II molecules but independent of NKG2D; immunization with recombinant MICA elicited a predominantly Th2-type CD4+ T cell response (IL-4 dominant), and MICA-stimulated CD8+ T cells killed MICA-primed target cells. Mouse immunization with rMICA, [3H]thymidine proliferation assay, CFSE proliferation tracking, cytokine ELISA, MHC class I/II and NKG2D blocking antibodies, cytotoxicity assay Human immunology Medium 16698445
2013 Endothelial cell MICA expression and shedding are regulated by inflammatory cytokines and proliferative signals: TNFα upregulates surface MICA via NF-κB and MAPK pathways (JNK, ERK1/2, p38); IFNγ decreases surface MICA; both cytokines induce soluble MICA release; FGF-2-driven EC proliferation and wound healing increase surface MICA levels. Glycosylation and metalloproteinase activity are major post-transcriptional mechanisms controlling MICA on ECs. Cytokine treatment of ECs, NF-κB and MAPK pathway inhibitors, metalloproteinase inhibitors, glycosylation inhibitors, flow cytometry for surface MICA, ELISA for soluble MICA, proliferation assays Journal of innate immunity Medium 23860405
2010 IL-2 induces MICA expression in T lymphocytes through signaling pathways involving Jak3/STAT5, p38 MAPK, p70S6 kinase, Lck/Fyn kinases, and NF-κB, as demonstrated by targeted pharmacological inhibition of each pathway. Pharmacological inhibition of Jak3, STAT5, p38 MAPK, p70S6K, Lck/Fyn, and NF-κB in IL-2-stimulated T cells; Western blot for MICA protein Human immunology Medium 16698439

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 542 15357948
2018 Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science (New York, N.Y.) 387 29599246
2008 Tumor-associated MICA is shed by ADAM proteases. Cancer research 307 18676862
1996 DNA binding to mica correlates with cationic radius: assay by atomic force microscopy. Biophysical journal 238 8785352
2003 Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. International journal of cancer 196 12569559
2003 MICA/NKG2D-mediated immunogene therapy of experimental gliomas. Cancer research 171 14695218
2001 MICA and MICB genes: can the enigma of their polymorphism be resolved? Trends in immunology 161 11429322
1999 Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Human immunology 122 10363723
2020 NKG2D and MICA/B shedding: a 'tag game' between NK cells and malignant cells. Clinical & translational immunology 121 33363734
2005 Exosomes and the MICA-NKG2D system in cancer. Blood cells, molecules & diseases 120 15885603
1997 AFM analysis of DNA-protamine complexes bound to mica. Nucleic acids research 119 9153324
2001 MICA polymorphism is associated with type 1 diabetes in the Korean population. Diabetes care 111 11194237
2007 The relationship of anti-MICA antibodies and MICA expression with heart allograft rejection. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 94 17511763
2013 Mica functionalization for imaging of DNA and protein-DNA complexes with atomic force microscopy. Methods in molecular biology (Clifton, N.J.) 92 23027008
2010 MicA sRNA links the PhoP regulon to cell envelope stress. Molecular microbiology 91 20345657
2007 Sigma E controls biogenesis of the antisense RNA MicA. Nucleic acids research 90 17267407
2009 MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease. Blood 86 19786616
2010 MICA polymorphism: biology and importance in immunity and disease. Trends in molecular medicine 83 20153697
2007 In vivo expression pattern of MICA and MICB and its relevance to auto-immunity and cancer. PloS one 83 17565371
1999 Association of MICA gene and HLA-B*5101 with Behçet's disease in Greece. Investigative ophthalmology & visual science 76 10440244
2014 MICA polymorphism: biology and importance in cancer. Carcinogenesis 74 25330802
2015 The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation. EMBO molecular medicine 69 26483398
2008 Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB. The Journal of cell biology 68 18644891
2002 Activation-induced expression of MICA on T lymphocytes involves engagement of CD3 and CD28. Journal of leukocyte biology 68 11994503
2010 Regulation of the small regulatory RNA MicA by ribonuclease III: a target-dependent pathway. Nucleic acids research 67 21138960
2001 Two distinct MICA gene markers discriminate major autoimmune diabetes types. The Journal of clinical endocrinology and metabolism 66 11502807
2002 MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of rheumatology 58 12022360
2011 NF-κB regulates MICA gene transcription in endothelial cell through a genetically inhibitable control site. The Journal of biological chemistry 54 22170063
2012 Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner. International journal of oncology 51 22992985
2019 Imaging DNA Equilibrated onto Mica in Liquid Using Biochemically Relevant Deposition Conditions. ACS nano 48 30938988
2015 The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA. Immunogenetics 47 26585323
2010 Association analysis of MICA gene polymorphism and MICA-129 dimorphism with inflammatory bowel disease susceptibility in a Spanish population. Human immunology 45 20152875
2001 Diversity of MICA (PERB11.1) and HLA haplotypes in Northeastern Thais. Tissue antigens 45 11696220
2016 Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks. Frontiers in immunology 44 28018354
2014 MICA SNPs and the NKG2D system in virus-induced HCC. Journal of gastroenterology 44 25270965
2013 HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 44 24075503
2001 MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Tissue antigens 44 11782275
2017 Major Histocompatibility Complex Class I Chain-Related A (MICA) Molecules: Relevance in Solid Organ Transplantation. Frontiers in immunology 43 28293239
2013 MICA, a gene contributing strong susceptibility to ankylosing spondylitis. Annals of the rheumatic diseases 43 23727634
2014 c-Cbl regulates MICA- but not ULBP2-induced NKG2D down-modulation in human NK cells. European journal of immunology 42 24846123
2016 A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma. Cancer letters 41 26791237
2018 MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma. Frontiers in immunology 40 29765374
2022 MICA/B antibody induces macrophage-mediated immunity against acute myeloid leukemia. Blood 39 34359073
2022 The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation. Nature medicine 38 35288692
2013 Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs. Scientific reports 38 24061441
2012 Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding. Cancer immunology, immunotherapy : CII 38 22215138
2000 Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes. Journal of pediatric endocrinology & metabolism : JPEM 38 10803866
2009 MICA polymorphisms and decreased expression of the MICA receptor NKG2D contribute to idiopathic pulmonary fibrosis susceptibility. Human genetics 37 19363685
2020 High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies. Frontiers in immunology 36 32153595
2019 Catalytic, kinetic and thermodynamic properties of free and immobilized caseinase on mica glass-ceramics. Heliyon 35 31193050
2011 Association of MICA and MICB alleles with symptomatic dengue infection. Human immunology 34 21762746
2008 Relationship between soluble MICA and the MICA A5.1 homozygous genotype in patients with oral squamous cell carcinoma. Clinical immunology (Orlando, Fla.) 34 18951065
2020 Tumor-Derived Soluble MICA Obstructs the NKG2D Pathway to Restrain NK Cytotoxicity. Aging and disease 33 32010486
2008 Allelic diversity of MICA gene and MICA/HLA-B haplotypic variation in a population of the Murcia region in southeastern Spain. Human immunology 33 18718856
1998 MICA gene polymorphism in Takayasu's arteritis and Buerger's disease. International journal of cardiology 33 9951809
2006 Intracellular expression of MICA in activated CD4 T lymphocytes and protection from NK cell-mediated MICA-dependent cytotoxicity. Human immunology 32 16698439
2018 Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells. International journal of cancer 31 29873070
2013 MICA variant promotes allosensitization after kidney transplantation. Journal of the American Society of Nephrology : JASN 31 23539759
2010 Role of MICA in the immune response to transplants. Tissue antigens 31 20696027
2002 Further polymorphism of the MICA gene. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 30 11841487
2005 NKG2D-independent suppression of T cell proliferation by H60 and MICA. Proceedings of the National Academy of Sciences of the United States of America 29 16091471
2023 MUC1-C is a master regulator of MICA/B NKG2D ligand and exosome secretion in human cancer cells. Journal for immunotherapy of cancer 28 36754452
2013 Role of HLA, KIR, MICA, and cytokines genes in leprosy. BioMed research international 28 23936864
2011 Expression of MICA, MICB and NKG2D in human leukemic myelomonocytic and cervical cancer cells. Journal of experimental & clinical cancer research : CR 28 21477352
2010 Interleukin 10 decreases MICA expression on melanoma cell surface. Immunology and cell biology 28 20714339
2015 Study of DNA adsorption on mica surfaces using a surface force apparatus. Scientific reports 26 25676333
2013 Endothelial cell activation and proliferation modulate NKG2D activity by regulating MICA expression and shedding. Journal of innate immunity 26 23860405
1999 MICA gene polymorphism and the risk to develop cervical intraepithelial neoplasia. Human immunology 26 10566597
2020 Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein. Journal for immunotherapy of cancer 25 32518090
2017 Purine nucleotide metabolism regulates expression of the human immune ligand MICA. The Journal of biological chemistry 25 29279329
2010 Specific DNA-protein interactions on mica investigated by atomic force microscopy. Langmuir : the ACS journal of surfaces and colloids 25 19791748
2007 Mutations designed to destabilize the receptor-bound conformation increase MICA-NKG2D association rate and affinity. The Journal of biological chemistry 25 17690100
2007 MICA gene polymorphism in the pathogenesis of type 1 diabetes. Annals of the New York Academy of Sciences 25 17911424
2006 MICA antigens stimulate T cell proliferation and cell-mediated cytotoxicity. Human immunology 25 16698445
2006 Post-transplant soluble MICA and MICA antibodies predict subsequent heart graft outcome. Transplant immunology 25 17157214
2006 HLA and MICA associations with head and neck squamous cell carcinoma. Oral oncology 23 16857416
2004 Polymorphism of the MICA gene and risk for oral submucous fibrosis. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 23 14675133
2014 Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes. Tissue antigens 21 24962621
2009 Expression of HLA-G and MICA mRNA in renal allograft. Transplant immunology 21 19193353
2008 Estradiol regulates MICA expression in human endometrial cells. Clinical immunology (Orlando, Fla.) 21 18728002
2019 LINC01149 variant modulates MICA expression that facilitates hepatitis B virus spontaneous recovery but increases hepatocellular carcinoma risk. Oncogene 20 31754211
2011 MICB polymorphisms and haplotypes with MICA and HLA alleles in Koreans. Tissue antigens 20 21554252
2004 MICA and recovery from hepatitis C virus and hepatitis B virus infections. Genes and immunity 20 15029237
2020 Leukotriene receptor antagonists enhance HCC treatment efficacy by inhibiting ADAMs and suppressing MICA shedding. Cancer immunology, immunotherapy : CII 19 32683508
2013 Role of MICA antibodies in solid organ transplantation. Clinical transplantation 18 24372774
2009 MICA polymorphisms and haplotypes with HLA-B and HLA-DRB1 in Koreans. Tissue antigens 18 19895570
2007 MICA and MICB overexpression in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 18 17181741
2022 αVEGFR2-MICA fusion antibodies enhance immunotherapy effect and synergize with PD-1 blockade. Cancer immunology, immunotherapy : CII 17 36227341
2021 The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing. PLoS pathogens 17 33939764
2018 5-Methoxyindole-2-carboxylic acid (MICA) suppresses Aβ-mediated pathology in C. elegans. Experimental gerontology 17 29709515
2013 HLA and MICA polymorphism in Polynesians and New Zealand Maori: implications for ancestry and health. Human immunology 17 23792058
2003 Up-regulated expression of MICA and proinflammatory cytokines in skin biopsies from patients with seborrhoeic dermatitis. Clinical immunology (Orlando, Fla.) 17 12584051
2023 MICA: a multi-omics method to predict gene regulatory networks in early human embryos. Life science alliance 16 37879938
2018 NKG2D Immunoligand rG7S-MICA Enhances NK Cell-mediated Immunosurveillance in Colorectal Carcinoma. Journal of immunotherapy (Hagerstown, Md. : 1997) 16 29528990
2017 Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system. Biochemical and biophysical research communications 16 28322797
2015 MICA polymorphisms and cancer risk: a meta-analysis. International journal of clinical and experimental medicine 16 25785062
2015 Associations of MICA Polymorphisms with Inflammatory Rheumatic Diseases. The open rheumatology journal 16 26862354
2005 Distinct pattern of human Vdelta1 gammadelta T cells recognizing MICA. Cellular & molecular immunology 16 16274622
2014 MICA/B expression in macrophage foam cells infiltrating atherosclerotic plaques. Experimental and molecular pathology 15 24997223
2002 The increase in the frequency of MICA gene A6 allele in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 15 12190814

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