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Query: UNIPROT:Q29983 (MIC)
 21,138 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major histocompatibility complex (MHC) class I genes typically encode polymorphic peptide-binding chains which are ubiquitously expressed and mediate the recognition of intracellular antigens by cytotoxic T cells. They constitute diverse gene families in different species and include the numerous so-called nonclassical genes in the mouse H-2 complex, of which some have been adapted to variously modified functions. We have identified a distinct family of five related sequences in the human MHC which are distantly homologous to class I chains. These MIC genes (MHC class I chain-related genes) evolved in parallel with the human class I genes and with those of most if not all mammalian orders. The MICA gene in this family is located near HLA-B and is by far the most divergent mammalian MHC class I gene known. It is further distinguished by its unusual exon-intron organization and preferential expression in fibroblasts and epithelial cells. However, the presence of diagnostic residues in the MICA amino acid sequence translated from cDNA suggests that the putative MICA chain folds similarly to typical class I chains and may have the capacity to bind peptide or other short ligands. These results define a second lineage of evolutionarily conserved MHC class I genes. This implies that MICA and possibly other members in this family have been selected for specialized functions that are either ancient or derived from those of typical MHC class I genes, in analogy to some of the nonclassical mouse H-2 genes.
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PMID:A second lineage of mammalian major histocompatibility complex class I genes. 802 69

Major histocompatibility complex (MHC) class I chain-related genes, MICA and MICB, are located centromeric to human leukocyte antigen B (HLA-B) on chromosome 6. In response to stress stimuli, MIC is expressed on epithelial, endothelial and fibroblast cells, but not lymphocytes and has been demonstrated to ligate the natural killer (NK) cell receptor, NKG2D. Nucleotide sequences of MICA and MICB are highly polymorphic and several methods have been established to identify these polymorphisms, including sequence-based typing and sequence-specific oligonucleotide probing. In this study we have developed a high-resolution polymerase chain reaction-sequence-specific primer (PCR-SSP) phototyping scheme that detects all WHO-recognized MICA alleles and all 12 MICB alleles. Our method will also recognize a MICA deletion haplotype and distinguish between MICA alleles with different binding affinities for NKG2D, encoded by a non-synonymous nucleotide substitution in codon 129. Furthermore, our scheme targets almost 90% of the dimorphic codon positions in exons 2, 3, and 4, which result in non-synonymous amino acid changes. This method can be used to determine MIC allele frequencies within different populations, as well as investigate MIC associations in cohorts of patients with autoimmune and infectious diseases and explore the impact of MIC on the survival of solid organ and stem cell transplants.
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PMID:High resolution molecular phototyping of MICA and MICB alleles using sequence specific primers. 1217 34

Major histocompatibility complex (MHC) class I chain related gene-A (MIC-A) is associated with type 1 diabetes mellitus (T1DM) in other populations. We tested the association of MIC-A gene polymorphism with T1DM in Swedish Caucasians; if it has an age-dependent association; and if the association has an effect on gender. We studied 635 T1DM patients and 503 matched controls in the age group of 0-35 years old. MIC-A5 was significantly increased in T1DM compared with controls (odds ratio [OR] =1.81, p(c) < 0.0005). Logistic regression analysis revealed MIC-A5 association was independent of HLA. MIC-A5 with DR4-DQ8 or MIC-A5 with DR3-DQ2 gave higher OR than the OR obtained with either of them alone (OR = 1.81, 7.1, and 3.6, respectively). MIC-A5 was positively (OR = 2.48, p(c) < 0.0005) and MIC-A6 negatively associated (OR = 0.61, p(c) = 0.035) with the disease in < or = 20 years of age. The negative association of MIC-A6 in young onset was confirmed by logistic regression analysis. MIC-A5 was associated with the disease in males (OR = 2.05, p(c) = 0.0005). MIC-A6 conferred protection (OR = 0.098, p(c) = 0.032) in females heterozygous for DR3/DR4. In conclusion, MIC-A5 is associated with T1DM; the association was higher in individuals < or = 20 years old; and negative association of MIC-A6 was stronger in younger onset patients than in older onset patients.
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PMID:Association between the transmembrane region polymorphism of MHC class I chain related gene-A and type 1 diabetes mellitus in Sweden. 1269 6

Major histocompatibility complex (MHC) class I chain related (MIC) molecules show homology with classical human leukocyte antigen (HLA) molecules, but they do not combine with beta2 microglobulin, do not bind peptide and are not expressed on normal circulating lymphocytes. In response to stress, MIC proteins are expressed on the cell surface of freshly isolated gastric epithelium, endothelial cells and fibroblasts and engage the activating natural killer cell receptor NKG2D, which is found on many cells within the immune system. Despite the highly polymorphic nature of MIC genes, only one polymorphic position has been identified that appears to affect the binding of NKG2D. Alleles with a methionine at codon 129 have a 10-50-fold greater capacity to complex NKG2D than alleles with a valine at this position. Renal and pancreatic grafts with evidence of both acute and chronic rejection have been shown to express MIC proteins, and anti-MIC antibodies have been identified in the serum of these patients. Some MIC molecules which are expressed by tumours appear to shed and solubilize in plasma. This soluble form of MIC engages cells expressing NKG2D, rendering them inactive, and impairs tumour cytolysis. Similarly, a protein encoded by human cytomegalovirus (CMV) prevents MICB surface expression and subsequent NKG2D interaction. Whereas the benefit of solid organ transplantation may be hindered by the expression of MIC molecules on grafts, tumours and viruses may take advantage of the expression of MIC molecules on transformed and virus-infected cells in order to evade this recognition pathway.
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PMID:Human MHC class I chain related (MIC) genes: their biological function and relevance to disease and transplantation. 1518 23

Major histocompatibility complex (MHC) class I molecules comprise a family of polymorphic cell surface receptors consisting of classical 1 a molecules that present antigenic peptides and nonclassical 1 b molecules. Gene expression for human classical and nonclassical MHC class I molecules has been shown to be differentially regulated by interferon, with variation in the nucleotide sequence of promoter regions, resulting in differences in interferon inducibility and basal levels of gene transcription. In this study on porcine classical and nonclassical swine leukocyte Ag (SLA) class I molecules, we show alignments of putative regulatory elements in the promoters of the three functional classical class I genes, SLA-1, SLA-2, and SLA-3; two nonclassical 1 b genes, SLA-6 and SLA-7; and a MIC-2 gene. Promoter elements were cloned upstream from a luciferase reporter gene, and the basal and inducible activities of each were characterized by expression in Max cells, an immortalized pig cell line that responds to interferon and tumor necrosis factor alpha (TNF-alpha). All three classical class I but not nonclassical promoters responded to interferon. This was confirmed by the transactivation of SLA-1, but not SLA-7, after the co expression with interferon regulatory factors (IRFs), IRF-1, IRF-2, IRF-3, IRF-7, and IRF-9. Classical class I genes were activated by cotransfection with nuclear factor kappa B (NF-kappaB) p65 and by treatment of cells with TNF-alpha, although, unlike human promoter there was no synergistic effect with interferon. The greatest effect on classical class I promoters was coexpression with the class II transactivator (CIITA), important for constitutive transactivation. These results determine the differential regulation of porcine classical and nonclassical MHC class I and reflects their importance in antigen presentation during infection.
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PMID:Regulation of porcine classical and nonclassical MHC class I expression. 1735 69

Major histocompatibility complex (MHC) class I chain-related (MIC) genes have been previously identified and characterised in human. They encode polymorphic class I-like molecules that are stress-inducible, and constitute one of the ligands of the activating natural killer cell receptor NKG2D. We have identified three MIC genes within the cattle genome, located close to three non-classical MHC class I genes. The genomic position relative to other genes is very similar to the arrangement reported in the pig MHC region. Analysis of MIC cDNA sequences derived from a range of cattle cell lines suggest there may be four MIC genes in total. We have investigated the presence of the genes in distinct and well-defined MHC haplotypes, and show that one gene is consistently present, while configuration of the other three genes appears variable.
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PMID:Genomic location and characterisation of MIC genes in cattle. 1854 44

Major histocompatibility complex (MHC) class I chain-related gene A (MICA), a ligand for the activating immunoreceptor natural killer group 2D (NKG2D), is expressed on stressed cells such as tumor cells. Study of expression of this molecule on tumor cells and patients' sera is useful to define patients' stages leading to proper selection of therapy. In this study, mouse anti-MICA monoclonal antibodies (mAbs) were produced by DNA immunization using a gene gun. Screening of anti-MICA-producing mouse and hybridomas were performed by immunoblot and cell enzyme-linked immunosorbent assay (ELISA) against MICA-positive HeLa and -negative Me1386 cell lines. MAbs were characterized against MICA-positive and -negative cell lines by immunoblot, cell ELISA and flow cytometry. The mAbs were also characterized for locus and allele specificities of MICA and MHC class I chain-related gene B (MICB) as well as for their ability to stain formalin-fixed paraffin-embedded tissues by immunohistochemistry. Although all mouse immune sera were positive with MICA-positive cells by both immunoblot and cell ELISA methods, some hybridomas were positive only with one method. The mAbs had diverse specificities to detect MICA and MICB and different abilities to stain formalin-fixed paraffin-embedded tissues. Thus, DNA immunization by gene gun is an effective method to generate immune mice for the production of mAbs with a variety of specificities against native and denatured forms of MIC proteins.
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PMID:Production and characterization of monoclonal antibodies against major histocompatibility complex class I chain-related gene A. 1893 90

Major histocompatibility complex (MHC) class I chain-related (MIC) genes encode molecules that are expressed in response to stress, signalling immune system cells primarily via the activating receptor NKG2D. We investigated the expression of receptors for MIC in lymphocyte subsets found in peripheral blood, lymph node and gut in cattle and demonstrated their presence on natural killer (NK) cells, gammadelta T cells and CD8(+) T cells. Recognition of MIC by NKG2D was formally demonstrated using recombinant protein and an ELISA. Staining with a cross-reactive monoclonal antibody recognising both human and cattle MIC showed that MIC is constitutively expressed within cattle intestinal epithelium. A functional response to soluble MIC was observed in receptor-bearing cells in blood, lymph node and gut, the latter requiring relatively high levels of MIC to trigger a response. Results suggest that NKG2D is a functionally important activating receptor in cattle.
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PMID:Cattle MIC is a ligand for the activating NK cell receptor NKG2D. 2039 6

In this study, we investigate the relationship between natural killer (NK) cell susceptibility and the surface markers of cancer cells. Through phenotypic analysis, we found evidence that more susceptible cancer cell lines (K562 and Jurkat) express more NKG2D ligands. Major histocompatibility complex (MHC) class I chain-related A/B (MIC-A/B) and UL16 binding protein (ULBP) 1-5 molecules are typical ligands of NKG2D. The high killing activity of NK cells against K562 was abolished through the addition of a NKG2D blocking antibody. Upon in vitro stimulation with quercetin, low susceptible cancer cells increased NKG2D ligand expression, leading to enhancement of NK cell cytolytic activity. These results suggested that the anti-cancer activity of NK cells is not dependent on the origin and growth style of the target cells, but is dependent on the surface markers of the target cells.
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PMID:Importance of NKG2D-NKG2D ligands interaction for cytolytic activity of natural killer cell. 2261 8

Major histocompatibility complex class 1 chain-related gene sequence A is a polymorphic gene found at about 46.6 kb centromeric to HLA-B. It encodes a transmembrane protein, which is a non-classical human leukocyte antigen whose expression is normally induced by stress conditions like cancer and viral infections. The expression of MIC-A leads to the activation of NKG2D receptors of natural killer and T cells, leading to the generation of innate immune response that can easily eliminate/cleanse tumour cells and other cells that express the protein. Several bioinformatics and immunoinformatics tools were used to analyse the sequence and structure of the MIC-A protein. These tools were used in building and evaluating modelled structure of MIC-A, and to predict several antigenic determinant sites on the protein. The MIC-A protein structure generated an average antigenic propensity of 1.0289. Additionally, the hydrophilic regions on the surface of the MIC-A protein where antibodies can be attached were revealed. A total of fourteen antigenic epitopes were predicted, with six found in the transmembrane protein topology, and are predicted to play a role in the development of vaccines that can reactivate the functionalities of the MIC-A protein on the surface of cancer cells in order to elicit a desired immune response.
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PMID:Structural Analysis and Epitope Prediction of MHC Class-1-Chain Related Protein-A for Cancer Vaccine Development. 2929 63


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