Affinage

MICB

MHC class I polypeptide-related sequence B · UniProt Q29980

Length
383 aa
Mass
42.6 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICB is a stress-inducible MHC class I-related cell surface glycoprotein that functions as an activating ligand for the immunoreceptor NKG2D, engaging gamma-delta T cells, NK cells, and CD8+ T cells to trigger cytotoxicity against stressed and transformed cells (PMID:10359807, PMID:11491531, PMID:16849432). NKG2D homodimers bind monomeric MICB directly, and at the cytotoxic immune synapse MICB on target cells clusters NKG2D into the central supramolecular activation cluster, with bidirectional intercellular transfer of both molecules tuning the NK cytotoxic response (PMID:11491531, PMID:16849432). MICB expression is controlled at multiple regulatory layers. Transcriptionally, the MICB promoter is driven by Sp1/Sp3/Sp4 at a GC box and NF-Y at a CCAAT box, and is modulated by chromatin state, since HDAC inhibition raises histone H3 acetylation and lowers HDAC1 occupancy at the promoter, while promoter demethylation also induces expression (PMID:17557375, PMID:17625602, PMID:18395517); genotoxic stress couples MICB induction to the ATM/ATR/CHK1 DNA damage response (PMID:18644891, PMID:30483783). Post-transcriptionally, MICB mRNA is repressed by RNA-binding proteins acting through its 5'UTR (vigilin) and by IMP3, and by numerous miRNAs—including functionally convergent herpesviral miRNAs (HCMV, KSHV, EBV) and cellular miRNAs such as miR-10b—targeting its 3'UTR and 5'UTR (PMID:28356383, PMID:26982091, PMID:19380116, PMID:22915757, PMID:28850101). At the protein level, MICB is shed from the cell surface by metalloproteases including ADAM15 and the ADAM17/TIMP3 axis, generating soluble MICB that contributes to immune evasion; antibodies blocking the shedding site preserve surface MICB and reactivate NK antitumor immunity in vivo (PMID:23314034, PMID:28404876, PMID:16698441, PMID:29599246). Viral immunoevasins additionally subvert MICB: HCMV UL16 engages the alpha-helical platform domain via a glutamine-169-dependent interface that mimics the NKG2D binding mode and retains MICB intracellularly, with allelic MICB variants differing in UL16 binding (PMID:20090832, PMID:23625227). A naturally occurring MICB D136N missense variant reduces surface expression and NKG2D ligation, blunting NK killing (PMID:37878820).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    Established MICB as a stress-induced cell surface ligand recognized by the immune system, defining its role in immune surveillance of tumors independent of peptide presentation.

    Evidence Vdelta1 gamma-delta T cell recognition assays against autologous and heterologous tumor cells expressing MICA/B

    PMID:10359807

    Open questions at the time
    • Did not identify the activating receptor responsible for recognition
    • Did not resolve how MICB induction is triggered
  2. 2001 High

    Identified NKG2D as the receptor binding MICB directly, providing the molecular basis for MICB-driven immune activation.

    Evidence Solution binding of NKG2D homodimers to MICA, soluble NKG2D binding to surface MICB, allelic variant comparison

    PMID:11491531

    Open questions at the time
    • Affinity and structural detail of NKG2D-MICB itself not fully quantified
    • Downstream signaling consequences not addressed
  3. 2006 High

    Showed MICB engagement at the NK immune synapse drives NKG2D clustering and bidirectional transfer, revealing a self-limiting feature of MICB-mediated activation, while metalloprotease shedding generates soluble MICB in patient sera.

    Evidence Live synapse imaging, cytotoxicity assays with MICB-expressing target cells; metalloprotease inhibitor assays and serum ELISA

    PMID:16698441 PMID:16849432

    Open questions at the time
    • Identity of the shedding metalloprotease not defined
    • Functional consequence of soluble MICB on NK cells unclear (no NKG2D downregulation observed)
  4. 2007 High

    Defined the transcriptional architecture of the MICB promoter (Sp1/NF-Y) and demonstrated chromatin-level control via histone acetylation and HDAC1 occupancy.

    Evidence Promoter reporter assays, EMSA, promoter polymorphism analysis; ChIP for H3 acetylation and HDAC1 at the MICB promoter

    PMID:17557375 PMID:17625602

    Open questions at the time
    • Signals that recruit HDAC1 versus activators not defined
    • Connection between promoter occupancy and physiological stress unaddressed
  5. 2008 High

    Placed MICB induction downstream of the ATM/ATR/CHK1 DNA damage response and linked it to promoter demethylation, establishing genotoxic stress as a trigger of MICB surface expression.

    Evidence Dicer knockdown with ATM/ATR/CHK1 inhibition; 5-aza-dC treatment with bisulfite sequencing and ATM inhibition

    PMID:18395517 PMID:18644891

    Open questions at the time
    • Molecular step coupling DDR kinases to MICB transcription not identified
    • Relative contribution of transcriptional versus post-transcriptional DDR control unresolved
  6. 2009 High

    Revealed convergent post-transcriptional immune evasion: structurally unrelated herpesviral miRNAs target the MICB 3'UTR to suppress NK recognition during infection.

    Evidence MICB 3'UTR reporter assays, authentic HCMV/KSHV/EBV infection, NK killing assays

    PMID:19380116

    Open questions at the time
    • Selective pressure driving 3'UTR targeting not defined
    • Interplay with host miRNA regulation unaddressed
  7. 2010 High

    Defined at atomic resolution how the HCMV UL16 immunoevasin captures MICB via the NKG2D-mimicking platform domain, pinpointing glutamine-169 as the allele-specific determinant.

    Evidence X-ray crystallography at 1.8 A, surface plasmon resonance, mutational analysis

    PMID:20090832

    Open questions at the time
    • Intracellular retention mechanism downstream of binding not structurally resolved
    • Generalizability to other immunoevasins not established here
  8. 2013 Medium

    Expanded the regulatory repertoire to specific sheddases and additional viral evaders, and established allele-dependent UL16 binding among MICB variants.

    Evidence ADAM15 knockdown with surface/soluble MICB measurement; HBsAg-induced miRNA profiling; HHV-7 U21 surface downregulation; allele-specific UL16 Fc-fusion binding assays

    PMID:22102813 PMID:23314034 PMID:23625227 PMID:23917076

    Open questions at the time
    • Whether multiple sheddases act redundantly on MICB unresolved
    • U21 lysosomal mechanism for MICB inferred from ULBP1, not directly shown
  9. 2016 Medium

    Identified RNA-binding proteins (including vigilin via the 5'UTR and IMP3) as direct post-transcriptional repressors of MICB linking RNA metabolism to NK evasion.

    Evidence RNA pull-down with mass spectrometry, knockdown, surface MICB flow cytometry, NK assays (multiple studies)

    PMID:24924487 PMID:26982091 PMID:28356383

    Open questions at the time
    • IMP3 effect on MICB is indirect and mechanistically undefined
    • Coordination among the multiple RBPs not established
  10. 2017 Medium

    Refined the spatial and signaling control of MICB, showing predominantly intracellular localization, STAT3- and PI3K/Akt-linked modulation, and extensive multi-miRNA targeting of both UTRs.

    Evidence Confocal microscopy of tumor/normal tissue; STAT3 and PI3K inhibitor studies with NK assays; dual-UTR luciferase reporters with binding-site mutagenesis

    PMID:24885711 PMID:28334733 PMID:28850101 PMID:28917678

    Open questions at the time
    • Mechanism routing MICB to the surface from intracellular pools not defined
    • Non-metalloprotease MICB secretion pathway uncharacterized
  11. 2018 High

    Established protein-level stabilization strategies and therapeutic proof-of-concept: blocking shedding or stabilizing MICB protein preserves surface ligand and reactivates antitumor immunity.

    Evidence Anti-alpha3-domain shedding-blocking antibodies in immunocompetent mice with NK depletion; miR-34a/ATR/E2F1 perturbations; (2019) LXR-driven lysosomal MICB stabilization

    PMID:29599246 PMID:30256916 PMID:31125275

    Open questions at the time
    • Lysosomal degradation machinery for MICB not molecularly defined
    • Context-dependence of miR-34a dual effect across tumor types unresolved
  12. 2020 Medium

    Demonstrated that natural MICB coding variation functionally tunes NKG2D ligation and NK killing, linking MICB genotype to immune outcomes.

    Evidence Expression of MICB D136N missense variant, surface flow cytometry, NKG2D activation and NK coculture killing assays

    PMID:37878820

    Open questions at the time
    • Molecular basis for reduced surface expression of D136N not defined
    • Population-level immune consequences not established mechanistically

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse transcriptional, RNA-binding, miRNA, shedding, and trafficking inputs are integrated to set MICB surface density on a given stressed cell remains unresolved.
  • No unified model coupling DDR signaling to specific surface-trafficking steps
  • Mechanism controlling intracellular retention versus surface display of MICB undefined
  • Relative quantitative contribution of each regulatory layer in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ADAM15ADAM17HDLBPIGF2BP3KLRK1SP1TIMP3UL16

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MICA and MICB are stress-induced ligands recognized by gamma delta T cells expressing Vdelta1 on tumor cells. Vdelta1 gamma delta T cell lines and clones derived from tumors recognized MICA/B on autologous and heterologous tumor cells without constraints imposed by specific peptide ligands. T cell recognition assays using tumor-derived Vdelta1 gamma delta T cell lines and clones against autologous and heterologous tumor cells expressing MICA/B Proceedings of the National Academy of Sciences of the United States of America High 10359807
2001 NKG2D homodimers form stable complexes with monomeric MICA in solution without requiring additional components, and soluble NKG2D also binds to cell surface MICB. MICA glycosylation is not essential but enhances complex formation. Allelic variants of MICA show large differences in NKG2D binding associated with a single amino acid substitution at position 129 in the alpha2 domain. Solution binding assay (NKG2D homodimers with monomeric MICA), cell surface binding of soluble NKG2D to MICB-expressing cells, allelic variant comparison Immunogenetics High 11491531
2006 MICB is shed by metalloproteases from tumor cells, generating soluble MICB detectable in sera of cancer patients. Cell-bound MICB causes downregulation of surface NKG2D on NK cells, but soluble MICB did not alter NKG2D expression on NK cells in vitro. Metalloprotease inhibitor assays, ELISA for soluble MICB in patient sera, NK cell NKG2D expression assays with soluble MICB Human immunology Medium 16698441
2006 NKG2D and MICB undergo intercellular transfer at the cytotoxic NK cell immune synapse (cNK-IS). MICB expressed on target cells induces clustering of NKG2D at the central supramolecular activation cluster. NKG2D transfer depended on binding to MICB. Transfer of MICB to NK cells also occurred, indicating bidirectional exchange. Brief interactions between NK cells and MICB-expressing target cells led to a reduction in NKG2D-dependent NK cytotoxicity. Live imaging of NK cell immune synapse, fluorescence microscopy, functional cytotoxicity assays with MICB-expressing 721.221 cells Proceedings of the National Academy of Sciences of the United States of America High 16849432
2007 HDAC inhibitor trichostatin A (TsA) increases MICA and MICB expression on leukemic cells by increasing histone H3 acetylation and decreasing HDAC1 association at the MICA and MICB promoters, as demonstrated by chromatin immunoprecipitation (ChIP) assay. ChIP assay for histone H3 acetylation and HDAC1 occupancy at MICA/MICB promoters; flow cytometry for surface expression; NK cytotoxicity assays Leukemia High 17625602
2007 The MICB promoter contains a CCAAT box binding NF-Y and a GC box binding Sp1, Sp3, and Sp4. A MICB promoter polymorphism involving a 2-bp deletion near the CCAAT box and GC box diminishes Sp1 transcriptional activation, reducing MICB promoter activity 18-fold. Transcriptional reporter assays, electrophoretic mobility shift assays (EMSA), functional analysis of promoter variants European journal of immunology High 17557375
2008 Knockdown of Dicer in human cells elicits DNA damage and upregulates MICB expression. Upregulation of MICB by Dicer knockdown is prevented by pharmacological or genetic inhibition of ATM, ATR, or CHK1 kinases, placing MICB upregulation downstream of the DNA damage response pathway. RNAi knockdown of Dicer, pharmacological and genetic inhibition of ATM/ATR/CHK1, qRT-PCR and flow cytometry for MICB expression The Journal of cell biology High 18644891
2008 5-Aza-2'-deoxycytidine (5-aza-dC) induces MICB expression through promoter DNA demethylation and DNA damage; ATM kinase inhibition partially prevents MICB upregulation, demonstrating that both DNA damage signaling and demethylation contribute to 5-aza-dC-induced MICB expression. 5-aza-dC treatment, bisulfite sequencing for promoter methylation, ATM inhibitor (KU55933) and ATM siRNA knockdown, flow cytometry Biochemical and biophysical research communications Medium 18395517
2009 microRNAs from multiple herpesviruses (HCMV, KSHV, EBV) directly target MICB mRNA at different but adjacent sites to repress its expression, enabling NK cell evasion. Despite no sequence homology among the viral miRNAs, they are functionally conserved in MICB suppression during authentic viral infection. Reporter assays with MICB 3'UTR, authentic viral infection experiments, NK cell killing assays Cell host & microbe High 19380116
2010 Crystal structure of HCMV UL16 in complex with MICB at 1.8 Å resolution reveals that UL16 uses a three-stranded beta-sheet to engage the alpha-helical surface of the MICB platform domain, mimicking the NKG2D binding mode. UL16 binds MICB with nanomolar affinity (12-66 nM, by SPR). The inability of UL16 to bind MICA is due to a single residue difference: glutamine at position 169 in MICB (versus arginine in MICA) is critical for UL16 binding. X-ray crystallography (1.8 Å), surface plasmon resonance binding assays, mutational analysis of key residues PLoS pathogens High 20090832
2011 HHV-7 U21 protein downregulates the surface expression of MICB (and MICA), resulting in reduction of NK-mediated cytotoxicity. U21 can bind to ULBP1 and reroute it to the lysosomal compartment; the mechanism of MICA/B downregulation may involve similar lysosomal redirection. Flow cytometry for surface MICB/MICA expression in U21-expressing cells, NK cytotoxicity assays PLoS pathogens Medium 22102813
2012 miR-10b directly binds the 3'UTR of MICB mRNA and downregulates MICB surface expression. Antagonizing miR-10b enhanced NKG2D-mediated NK killing of tumor cells in vitro and tumor clearance in vivo; overexpression of miR-10b downregulated MICB and impaired NK cell elimination of tumor cells. Luciferase reporter assays with MICB 3'UTR, miR-10b overexpression and antagonism, flow cytometry, in vitro and in vivo NK killing assays Cancer research High 22915757
2013 HBsAg overexpression in HepG2 cells induces cellular miRNAs that repress MICA and MICB expression by targeting their 3'UTRs. Inhibiting these HBsAg-induced miRNAs partially restores MICA/MICB expression and increases NK cell-mediated cytolysis of HCC cells. miRNA profiling, 3'UTR reporter assays, miRNA inhibitors, NK cell cytotoxicity assays Carcinogenesis Medium 23917076
2013 ADAM15 mediates MICB ectodomain shedding in PANC-1 pancreatic cancer cells. Knockdown of ADAM15 upregulates cell surface MICB and reduces soluble MICB in culture supernatant. Gemcitabine suppresses ADAM15 expression, leading to increased surface MICB and decreased soluble MICB without changing MICB mRNA levels. ADAM15 siRNA knockdown, flow cytometry for surface MICB, ELISA for soluble MICB, qRT-PCR, gemcitabine treatment Molecular medicine reports Medium 23314034
2014 Six RNA-binding proteins (RBPs) that bind and regulate MICB expression were identified by unbiased RNA pull-down combined with mass spectrometry. At least two of the identified RBPs function during genotoxic stress to regulate MICB. RNA pull-down with MICB mRNA, mass spectrometry, functional validation of RBP knockdowns during genotoxic stress Nature communications Medium 24924487
2014 Valproic acid (VPA), an HDAC inhibitor, upregulates MICA and MICB surface expression on pancreatic cancer cells via the PI3K/Akt signaling pathway. This effect is blocked by the PI3K inhibitor LY294002 or siRNA targeting PI3KCA, and sensitizes cancer cells to NK-mediated killing in vitro and in vivo. PI3K inhibitor treatment (LY294002), siRNA knockdown of PI3KCA, flow cytometry for MICB surface expression, qRT-PCR, NK cytotoxicity assays, xenograft experiments BMC cancer Medium 24885711
2016 The RNA-binding protein IMP3 directly interacts with ULBP2 mRNA to destabilize it, and indirectly targets MICB through a mechanistically distinct pathway. IMP3-mediated regulation of MICB leads to impaired NK cell recognition of transformed cells. RNA pull-down, mRNA stability assays, IMP3 knockdown and overexpression, flow cytometry for MICB surface expression, NK cell killing assays eLife Medium 26982091
2017 Vigilin, a multifunctional RNA-binding protein, binds to the 5'UTR of MICB mRNA and negatively regulates MICB expression. Vigilin knockdown in target cells increases MICB surface expression and enhances NK cell activation against those cells. RNA pull-down of MICB 5'UTR followed by mass spectrometry, vigilin knockdown, flow cytometry for MICB surface expression, NK cell activation assays Journal of immunology Medium 28356383
2017 STAT3 inhibition by STA21 increases MICB cell surface expression and soluble MICB secretion by gastric adenocarcinoma cells. Recombinant soluble MICB decreases NKG2D receptor levels on NK and CD8+ T cells and impairs their cytotoxic function. MICB shedding in this context was not affected by metalloprotease inhibition, suggesting a non-metalloprotease secretory pathway. STAT3 inhibitor (STA21) treatment, flow cytometry, ELISA for soluble MICB, metalloprotease inhibitor assays, NK cell cytotoxicity assays Immunobiology Medium 28917678
2017 MICB and MICA expression is predominantly intracellular in both tumor and normal tissue, with only occasional evidence of cell membrane localization. No qualitative differences in cell surface expression were observed between tumor and MICA/B-expressing normal epithelia. Standard and confocal immunofluorescence microscopy using well-characterized antibodies on multiple human tumor and normal tissue samples British journal of cancer Medium 28334733
2017 DAC (decitabine) treatment of AML cells increases TIMP3 expression by demethylation of its promoter, and TIMP3 (an ADAM17 inhibitor) inhibits shedding of MICB (and MICA and ULBP2), reducing soluble NKG2D ligands and enhancing NK cell-mediated immune recognition of AML cells. Hypomethylating agent treatment, ADAM17 inhibitor (TIMP3) overexpression, ELISA for soluble MICB, NK cell killing assays, methylation analysis Oncotarget Medium 28404876
2018 Antibodies targeting the MICA α3 domain (site of proteolytic shedding) prevent proteolytic shedding of both MICA and MICB from human cancer cells, maintain cell surface MICA/MICB, inhibit tumor growth in immunocompetent mouse models, and reactivate NK cell antitumor immunity via NKG2D and CD16 Fc receptors. Rational antibody design targeting α3 domain, flow cytometry for surface MICA/MICB, in vivo tumor growth assays in immunocompetent mice, NK cell depletion experiments, humanized mouse model Science High 29599246
2018 miR-34a plays a dual role in MICB regulation in hepatocytes: it can both increase MICB expression by upregulating ATR protein kinase and decrease MICB expression by downregulating the transcription factor E2F1. The net effect on MICB depends on endogenous E2F1 levels, with miR-34a promoting MICB in cells with low E2F1 (normal hepatocytes) but not in cells with high E2F1 (many HCC cells). miR-34a overexpression, ATR and E2F1 knockdown, flow cytometry, luciferase reporter assays, NK cell killing assays Carcinogenesis Medium 30256916
2018 MG132 (proteasome inhibitor) selectively upregulates MICB transcription in A549 lung cancer cells by acting at the 480-bp MICB upstream promoter. This upregulation requires ATM kinase, ATR kinase, and PI3K activity, as inhibitors of these kinases block MG132-induced MICB upregulation; MG132 activates CHK2 phosphorylation (a DNA damage marker), placing MICB upregulation downstream of the DNA damage response. MICB promoter luciferase reporter assay, ATM inhibitor (KU-55933), wortmannin, caffeine treatment, CHK2 phosphorylation assay, NK cytotoxicity blocking assays Molecular medicine reports Medium 30483783
2019 Liver X receptor (LXR) activation upregulates MICB expression in multiple myeloma cells through inhibition of MICB protein degradation in lysosomes (post-translational stabilization), whereas MICA is regulated at the transcriptional level. LXR activation enhances NK cell-mediated killing of MM cells. LXR agonist treatment, MICB protein stability assays with lysosomal inhibitors, MICA promoter activity assays, NK cell killing assays, flow cytometry FASEB journal Medium 31125275
2013 Diverse allelic MICB proteins differentially bind the HCMV immunoevasin UL16. MICB*008, which contains methionine and asparagine at positions 98 and 113 in the alpha2 domain, shows decreased binding to UL16 compared to MICB*003, *004, and *00502 (which contain isoleucine and aspartic acid at those positions). UL16 variant strains did not affect binding activities. Production of soluble Fc-fusion UL16 proteins from four HCMV strains, stable cell lines expressing four MICB alleles, flow cytometry-based binding assays Journal of microbiology Medium 23625227
2020 Missense variant MICB D136N (rs in MICB) expressed in cultured cells results in reduced surface MICB and reduced NKG2D ligation relative to wild-type MICB. Coculture of MICB D136N-expressing cells with NK cells results in less NKG2D activation and less susceptibility to NK cell killing compared to wild-type MICB-expressing cells. Expression of MICB missense variant protein in cultured cells, flow cytometry for surface MICB, NKG2D activation assays, NK cell coculture killing assays, ex vivo BAL analysis American journal of respiratory and critical care medicine Medium 37878820
2003 Transgenic mice ubiquitously expressing human MICB develop transient hyperkeratosis of the epidermis with infiltrating inflammatory cells, and a 50% increase in white blood cells, indicating that MICB expression in vivo is associated with skin inflammation and leukocytosis. Transgenic mouse generation with ubiquitous MICB promoter, histopathological analysis, complete blood count Tissue antigens Medium 12753668
2017 Nine novel miRNAs were identified that regulate MICB expression via both its 3'UTR and 5'UTR sequences in human cancer cells. Mutation of miRNA binding sites in both UTRs increased luciferase reporter activity, and overexpression/inhibition of candidate miRNAs decreased/increased MICB protein expression on cell surfaces. Luciferase reporter assays with MICB 3'UTR and 5'UTR constructs, site-directed mutagenesis of miRNA binding sites, miRNA overexpression and inhibition, flow cytometry Genes Medium 28850101

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proceedings of the National Academy of Sciences of the United States of America 832 10359807
2018 Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science (New York, N.Y.) 387 29599246
2009 Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell host & microbe 386 19380116
2001 Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics 377 11491531
2003 Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. International journal of cancer 196 12569559
2001 MICA and MICB genes: can the enigma of their polymorphism be resolved? Trends in immunology 161 11429322
2006 Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Human immunology 121 16698441
1999 Microsatellite polymorphism of the MHC class I chain-related (MIC-A and MIC-B) genes marks the risk for autoimmune Addison's disease. The Journal of clinical endocrinology and metabolism 120 10523017
2020 Inhibition of MICA and MICB Shedding Elicits NK-Cell-Mediated Immunity against Tumors Resistant to Cytotoxic T Cells. Cancer immunology research 112 32209637
2012 MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells. Cancer research 108 22915757
2006 Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA. Cancer immunology, immunotherapy : CII 104 16636811
2007 Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Leukemia 99 17625602
2017 MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue. British journal of cancer 92 28334733
2007 In vivo expression pattern of MICA and MICB and its relevance to auto-immunity and cancer. PloS one 83 17565371
2006 Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function. Proceedings of the National Academy of Sciences of the United States of America 74 16849432
1997 Allelic variants of the human MHC class I chain-related B gene (MICB). Immunogenetics 74 9321430
2008 Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB. The Journal of cell biology 68 18644891
2001 Competence repression under oxygen limitation through the two-component MicAB signal-transducing system in Streptococcus pneumoniae and involvement of the PAS domain of MicB. Journal of bacteriology 63 11443095
2002 MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of rheumatology 58 12022360
2007 Transcriptional regulation of MICA and MICB: a novel polymorphism in MICB promoter alters transcriptional regulation by Sp1. European journal of immunology 57 17557375
2014 Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway. BMC cancer 55 24885711
2008 Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine. Biochemical and biophysical research communications 53 18395517
2006 Expression of MHC class I-related Chain B (MICB) molecules on renal transplant biopsies. Transplantation 46 16641608
2016 The RNA binding protein IMP3 facilitates tumor immune escape by downregulating the stress-induced ligands ULPB2 and MICB. eLife 44 26982091
2001 MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Tissue antigens 44 11782275
2010 Structure of the HCMV UL16-MICB complex elucidates select binding of a viral immunoevasin to diverse NKG2D ligands. PLoS pathogens 43 20090832
2011 The human herpesvirus-7 (HHV-7) U21 immunoevasin subverts NK-mediated cytoxicity through modulation of MICA and MICB. PLoS pathogens 41 22102813
2001 Wide distribution of the MICA-MICB null haplotype in East Asians. Tissue antigens 41 11169252
2017 Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition. Oncotarget 39 28404876
2013 Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells. Carcinogenesis 39 23917076
2006 MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility. Rheumatology (Oxford, England) 37 17003176
2000 On the MICA deleted-MICB null, HLA-B*4801 haplotype. Tissue antigens 37 11034563
2002 High resolution molecular phototyping of MICA and MICB alleles using sequence specific primers. Human immunology 35 12175734
2011 Association of MICA and MICB alleles with symptomatic dengue infection. Human immunology 34 21762746
2007 Polymorphisms in MICB are associated with human herpes virus seropositivity and schizophrenia risk. Schizophrenia research 34 17561376
1998 Microsatellite polymorphism within the MICB gene among Japanese patients with Behçet's disease. Human immunology 34 9712354
2006 Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. Human molecular genetics 33 16923796
1998 Sequencing-based typing reveals six novel MHC class I chain-related gene B (MICB) alleles. Tissue antigens 32 9694358
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 Soluble MICB serum levels correlate with disease stage and survival rate in patients with oral squamous cell carcinoma. Anticancer research 28 21036725
2003 MICB typing by PCR amplification with sequence specific primers. Immunogenetics 28 12671735
2019 Activation of liver X receptor up-regulates the expression of the NKG2D ligands MICA and MICB in multiple myeloma through different molecular mechanisms. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 31125275
2014 A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1 in Thai patients with dengue shock syndrome. BMC medical genetics 27 24884822
2014 RNA-binding proteins regulate the expression of the immune activating ligand MICB. Nature communications 27 24924487
2005 The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy. Tissue antigens 27 16101831
2011 Characterization of the major histocompatibility complex class I chain-related gene B (MICB) polymorphism in a northern Chinese Han population: the identification of a new MICB allele, MICB*023. Human immunology 26 21664939
2010 HIF-1alpha accumulation upregulates MICA and MICB expression on human cardiomyocytes and enhances NK cell cytotoxicity during hypoxia-reoxygenation. Life sciences 25 20566410
2004 Association of MHC class I related gene B (MICB) to celiac disease. The American journal of gastroenterology 25 15089901
2002 Alu polymorphism within the MICB gene and association with HLA-B alleles. Immunogenetics 24 11862397
2008 Genetic influence of the nonclassical major histocompatibility complex class I molecule MICB in multiple sclerosis susceptibility. Tissue antigens 22 18588574
2017 5'-UTR and 3'-UTR Regulation of MICB Expression in Human Cancer Cells by Novel microRNAs. Genes 21 28850101
2016 MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population. Scandinavian journal of immunology 21 27028549
2014 Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes. Tissue antigens 21 24962621
2008 Associations of MICB with cervical cancer in north-eastern Thais: identification of major histocompatibility complex class I chain-related gene B motifs influencing natural killer cell activation. Clinical and experimental immunology 21 18505429
2011 MICB polymorphisms and haplotypes with MICA and HLA alleles in Koreans. Tissue antigens 20 21554252
2002 High frequency of MIC null haplotype (HLA-B48-MICA-del-MICB*0107 N) in the Angaite Amerindian community in Paraguay. Immunogenetics 20 12242594
2001 MICA and MICB microsatellite alleles in HLA extended haplotypes. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 20 11881819
2000 Three novel MICB alleles. Tissue antigens 19 10746790
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
2017 STAT3 inhibition by STA21 increases cell surface expression of MICB and the release of soluble MICB by gastric adenocarcinoma cells. Immunobiology 17 28578917
2012 MICB polymorphism in a southern Chinese Han population: the identification of two new MICB alleles, MICB*005:06 and MICB*026. Human immunology 17 22609444
2001 The nucleotide diversity of MICA and MICB suggests the effect of overdominant selection. Tissue antigens 17 11929594
2017 Soluble MICB in Plasma and Urine Explains Population Expansions of NKG2D+CD4 T Cells Inpatients with Juvenile-Onset Systemic Lupus Erythematosus. Open journal of immunology 14 28944101
2001 Linkage disequilibria between HLA-B, C1_4_1, MICA and MICB. Tissue antigens 14 11929593
2013 Distribution of MICB diversity in the Zhejiang Han population: PCR sequence-based typing for exons 2-6 and identification of five novel MICB alleles. Immunogenetics 13 23549730
2004 Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population. Tissue antigens 13 15304009
2020 Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status. Bone marrow transplantation 12 32286503
2006 MICB microsatellite polymorphism is associated with ulcerative colitis in Chinese population. Clinical immunology (Orlando, Fla.) 12 16679067
2002 Alternatively spliced forms of MICA and MICB lacking exon 3 in a human cell line and evidence of presence of similar RNA in human peripheral blood mononuclear cells. Immunogenetics 12 12466900
1999 Novel intronic variants of MICB (MHC class I chain-related gene B). European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 12 10583461
2018 MicroRNA-34a promotes MICB expression in hepatocytes. Carcinogenesis 11 30256916
2018 MG132 selectively upregulates MICB through the DNA damage response pathway in A549 cells. Molecular medicine reports 11 30483783
2016 MMP9 Promoter Polymorphism (-1562 C/T) Does not Affect the Serum Levels of Soluble MICB and MICA in Breast Cancer. Iranian journal of immunology : IJI 11 27026046
2013 ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells. Molecular medicine reports 11 23314034
2024 MICB Genomic Variant Is Associated with NKG2D-mediated Acute Lung Injury and Death. American journal of respiratory and critical care medicine 10 37878820
2021 High-throughput genotyping of HLA-G, HLA-F, MICA, and MICB and analysis of frequency distributions in healthy blood donors from Catalonia. HLA 10 33599111
2021 Associations of high-resolution-typing-defined MICA and MICB polymorphisms, and the levels of soluble MICA and MICB with Oral Squamous Cell Carcinoma in Bulgarian patients. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 9 33835601
2021 Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT. Journal of clinical medicine 9 34682758
2017 Vigilin Regulates the Expression of the Stress-Induced Ligand MICB by Interacting with Its 5' Untranslated Region. Journal of immunology (Baltimore, Md. : 1950) 9 28356383
2013 Metastamir-mediated immune evasion: miR-10b downregulates the stress-induced molecule MICB, hence avoid recognition by NKG2D receptor. Oncoimmunology 9 23479551
2004 Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients. Tissue antigens 9 15304008
2019 Inhibiting exosomal MIC-A and MIC-B shedding of cancer cells to overcome immune escape: new insight of approved drugs. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 8 31435903
2011 Impact of MICA-TM, MICB-C1_2_A and C1_4_1 microsatellite polymorphisms on the susceptibility to chronic periodontitis in Germany. Tissue antigens 8 21388352
2020 Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais. The Journal of infectious diseases 7 32737971
2013 Characterization of 3'untranslated region (3'UTR) of the MICB gene. Human immunology 7 23380144
2023 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 6 36958849
2022 HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population. Human immunology 6 35525711
2016 In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes. Functional & integrative genomics 6 27038471
2013 Allelic MHC class I chain related B (MICB) molecules affect the binding to the human cytomegalovirus (HCMV) unique long 16 (UL16) protein: implications for immune surveillance. Journal of microbiology (Seoul, Korea) 6 23625227
2018 MICB*002 and MICB*014 protect against rheumatoid arthritis, whereas MICA*009 and MICA*A6 are associated with rheumatoid arthritis in a Hainan Han Chinese population. International journal of rheumatic diseases 5 29665245
2016 Polymorphism rs3828903 within MICB Is Associated with Susceptibility to Systemic Lupus Erythematosus in a Northern Han Chinese Population. Journal of immunology research 5 27433477
2015 Soluble MICB protein levels and platelet counts during hepatitis B virus infection and response to hepatocellular carcinoma treatment. BMC infectious diseases 5 25626490
2003 Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB). Tissue antigens 5 12753668
2025 Identification of Novel MICB Alleles in Haematopoietic Stem Cell Donors of Indian Origin. HLA 4 39871443
2025 Downregulation of MICA/MICB improves cell persistence and clinical activity of NKG2DL CAR T-cells in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic neoplasia. Leukemia 4 40954213
2024 Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients. Journal of cellular biochemistry 4 38205878
2024 Entry into the lytic cycle exposes EBV-infected cells to NK cell killing via upregulation of the MICB ligand for NKG2D and activation of the CD56bright and NKG2A+KIR+CD56dim subsets. Frontiers in immunology 4 39676862
2023 Genetic Association Studies of MICB and PLCE1 with Severity of Dengue in Indonesian and Taiwanese Populations. Diagnostics (Basel, Switzerland) 4 37958261
2018 Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia. Viral immunology 4 30332343
2018 Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes. HLA 4 30471210

Missed literature

Know a paper Affinage missed for MICB? Flag it for the maintainers and the community.

No submissions yet.