The Experts below are selected from a list of 2883 Experts worldwide ranked by ideXlab platform
Alexander Steinle - One of the best experts on this subject based on the ideXlab platform.
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TGF-β and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells
Brain, 2006Co-Authors: Günter Eisele, Jörg Wischhusen, Alexander Steinle, Michel Mittelbronn, Richard Meyermann, Michael Weller, Inja Waldhauer, Manuel A. FrieseAbstract:NKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They transmit danger signals to NKG2D-expressing immune cells, leading to lysis of NKG2DL-expressing cells. We here report that the NKG2DL MHC class I-chain-related molecules A and B (MICA/B) and UL16-binding proteins (ULBP) 1–3 are expressed in human brain tumours in vivo , while expression levels are low or undetectable in normal brain. MICA and ULBP2 expression decrease with increasing WHO grade of malignancy, while MICB and ULBP1 are expressed independently of tumour grade. We further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-β (TGF-β) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-β or inhibition of MP. Thus, escape from NKG2D-mediated immune surveillance of malignant gliomas in vivo may be promoted by the inhibition of MICA and ULBP2 expression via an autocrine TGF-β loop and by MP-dependent shedding from the cell surface. Loss of MICA and ULBP2, in contrast to other NKG2DL, may be particularly important in glioma immune escape, and differential regulation of human NKG2DL expression is part of the immunosuppressive properties of human malignant glioma cells.
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Human Cytomegalovirus-Encoded UL16 Discriminates MIC Molecules by Their α2 Domains
Journal of Immunology, 2006Co-Authors: Jessica Spreu, Thilo Stehle, Alexander SteinleAbstract:Human CMV infection results in MHC class I down-regulation and induction of NKG2D ligand expression favoring NK recognition of infected cells. However, human CMV-encoded UL16 counteracts surface expression of several NKG2D ligands by intracellular retention. Interestingly, UL16 interacts with MICB, but not with the closely related MICA, and with UL16-binding proteins (ULBP) ULBP1 and ULBP2, which are only distantly related to MICB, but not with ULPB3 or ULBP4, although all constitute ligands for NKG2D. Here, we dissected the molecular basis of MICA-MICB discrimination by UL16 to elucidate its puzzling binding behavior. We report that the UL16-MICB interaction is independent of glycosylation and demonstrate that selective MICB recognition by UL16 is governed by helical structures of the MICB α2 domain. Transplantation of the MICB α2 domain confers UL16 binding capacity to MICA, and thus, diversification of the MICA α2 domain may have been driven by the selective pressure exerted by UL16.
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TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells.
Brain : a journal of neurology, 2006Co-Authors: Günter Eisele, Jörg Wischhusen, Alexander Steinle, Michel Mittelbronn, Richard Meyermann, Michael Weller, Inja Waldhauer, Manuel A. FrieseAbstract:NKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They transmit danger signals to NKG2D-expressing immune cells, leading to lysis of NKG2DL-expressing cells. We here report that the NKG2DL MHC class I-chain-related molecules A and B (MICA/B) and UL16-binding proteins (ULBP) 1-3 are expressed in human brain tumours in vivo, while expression levels are low or undetectable in normal brain. MICA and ULBP2 expression decrease with increasing WHO grade of malignancy, while MICB and ULBP1 are expressed independently of tumour grade. We further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or inhibition of MP. Thus, escape from NKG2D-mediated immune surveillance of malignant gliomas in vivo may be promoted by the inhibition of MICA and ULBP2 expression via an autocrine TGF-beta loop and by MP-dependent shedding from the cell surface. Loss of MICA and ULBP2, in contrast to other NKG2DL, may be particularly important in glioma immune escape, and differential regulation of human NKG2DL expression is part of the immunosuppressive properties of human malignant glioma cells.
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Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA
Cancer immunology immunotherapy : CII, 2006Co-Authors: Stefan Holdenrieder, Alexander Steinle, Petra Stieber, Andrea Peterfi, Dorothea Nagel, Helmut R. SalihAbstract:Expression of ligands of the immunoreceptor NKG2D such as MICA and MICB has been proposed to play an important role in the immunosurveillance of tumors. Proteolytic shedding of NKG2D ligands from cancer cells therefore constitutes an immune escape mechanism impairing anti-tumor reactivity by NKG2D-bearing cytotoxic lymphocytes. Serum levels of sMICA have been shown to be of diagnostic significance in malignant diseases of various origins. Here, we investigated the potential of soluble MICB, the sister molecule of MICA, as a marker in cancer and its correlation with soluble MICA. Analysis of MICB in sera of 512 individuals revealed slightly higher MICB levels in patients with various malignancies (N = 296; 95th percentile 216 pg/ml; P = 0.069) than in healthy individuals (N = 62; 95th percentile 51 pg/ml). Patients with benign diseases (N = 154; 95th percentile 198 pg/ml) exhibited intermediate MICB levels. In cancer patients, elevated MICB levels correlated significantly with cancer stage and metastasis (P = 0.007 and 0.007, respectively). Between MICB and MICA levels, only a weak correlation was found (r = 0.24). Combination of both markers resulted only in a slightly higher diagnostic power in the high specificity range. The reduction of MICA and MICB surface expression on cells by shedding and the effects of sMICA and sMICB in serum on host lymphocyte NKG2D expression might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. While MICB levels are not suited for the diagnosis of cancer in early stages, they may provide additional information for the staging of cancer disease.
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Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients.
Human immunology, 2006Co-Authors: Helmut R. Salih, Dennis Goehlsdorf, Alexander SteinleAbstract:MICA, a ligand of the activating immunoreceptor NKG2D, is released by tumor cells in a soluble form and can be detected in sera of tumor patients at significant levels. Soluble MICA has been proposed to counteract NKG2D-mediated immunosurveillance of tumors. Here, we report that MICB, the second member of the human MIC protein family, is likewise shed by metalloproteases from tumor cells and is present in sera of patients with gastrointestinal tumors. While cell-bound MICB causes downregulation of surface NKG2D, soluble MICB did not alter NKG2D expression on NK cells in vitro. Thus, proteolytic shedding of MICB by tumor cells may impair immunogenicity of tumors primarily by reducing NKG2D-ligand densities on malignant cells.
Charles H Yoon - One of the best experts on this subject based on the ideXlab platform.
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inhibition of mica and MICB shedding elicits nk cell mediated immunity against tumors resistant to cytotoxic t cells
Cancer immunology research, 2020Co-Authors: Jason Pyrdol, Charles H Yoon, Pedro Henrique Alves Da Silva, Lucas Ferrari De Andrade, Adrienne M Luoma, Sushil Kumar, Yoshinaga Ito, Deng PanAbstract:Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. Natural killer (NK) cells could potentially target such resistant tumors, but suitable NK-cell–based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a mAb that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface. The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NOD/SCID gamma mice reconstituted with human NK cells. NK-cell–mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells.
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inhibition of mica and MICB shedding elicits nk cell mediated immunity against tumors resistant to cytotoxic t cells
Cancer immunology research, 2020Co-Authors: Lucas Ferrari De Andrade, Jason Pyrdol, Charles H Yoon, Pedro Henrique Alves Da Silva, Adrienne M Luoma, Sushil Kumar, Kai W WucherpfennigAbstract:Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. NK cells could potentially target such resistant tumors, but suitable NK cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a monoclonal antibody (mAb) that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface. The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NSG mice reconstituted with human NK cells. NK cell-mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells.
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antibody mediated inhibition of mica and MICB shedding promotes nk cell driven tumor immunity
Science, 2018Co-Authors: Lucas Ferrari De Andrade, Sebastian Kobold, Jason Pyrdol, Charles H Yoon, Daphne Tsoucas, Adrienne M Luoma, Soumya Badrinath, Bettina Franz, Christopher HarveyAbstract:MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.
Lucas Ferrari De Andrade - One of the best experts on this subject based on the ideXlab platform.
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inhibition of mica and MICB shedding elicits nk cell mediated immunity against tumors resistant to cytotoxic t cells
Cancer immunology research, 2020Co-Authors: Jason Pyrdol, Charles H Yoon, Pedro Henrique Alves Da Silva, Lucas Ferrari De Andrade, Adrienne M Luoma, Sushil Kumar, Yoshinaga Ito, Deng PanAbstract:Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. Natural killer (NK) cells could potentially target such resistant tumors, but suitable NK-cell–based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a mAb that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface. The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NOD/SCID gamma mice reconstituted with human NK cells. NK-cell–mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells.
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inhibition of mica and MICB shedding elicits nk cell mediated immunity against tumors resistant to cytotoxic t cells
Cancer immunology research, 2020Co-Authors: Lucas Ferrari De Andrade, Jason Pyrdol, Charles H Yoon, Pedro Henrique Alves Da Silva, Adrienne M Luoma, Sushil Kumar, Kai W WucherpfennigAbstract:Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. NK cells could potentially target such resistant tumors, but suitable NK cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a monoclonal antibody (mAb) that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface. The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NSG mice reconstituted with human NK cells. NK cell-mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells.
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antibody mediated inhibition of mica and MICB shedding promotes nk cell driven tumor immunity
Science, 2018Co-Authors: Lucas Ferrari De Andrade, Sebastian Kobold, Jason Pyrdol, Charles H Yoon, Daphne Tsoucas, Adrienne M Luoma, Soumya Badrinath, Bettina Franz, Christopher HarveyAbstract:MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.
Wei Tian - One of the best experts on this subject based on the ideXlab platform.
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mica MICB polymorphisms and linkage disequilibrium with hla b in a chinese mongolian population
Scandinavian Journal of Immunology, 2016Co-Authors: W Y Wang, Wei Tian, Xuexiang Liu, F M Zhu, Fan WangAbstract:In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008 (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008 (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA-B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLA-linked disease association in populations of related ancestry.
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MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population.
Scandinavian journal of immunology, 2016Co-Authors: W Y Wang, Wei Tian, Xuexiang Liu, F M Zhu, Fan WangAbstract:In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P
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MICB polymorphism in a southern chinese han population the identification of two new MICB alleles MICB 005 06 and MICB 026
Human Immunology, 2012Co-Authors: Xuexiang Liu, Fenghua Pan, Wei TianAbstract:Abstract In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB ∗ 005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB ∗ 005:06 and MICB ∗ 026, were identified. Aligned with MICB ∗ 005:02, MICB ∗ 005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB ∗ 026 has probably arisen from MICB ∗ 004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A ∗ 02-C ∗ 01-B ∗ 46-MICA ∗ 010-MICB ∗ 005:02-DRB1 ∗ 09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A ∗ 30-C ∗ 06-B ∗ 13:02-MICA ∗ 008:01-MICB ∗ 005:02-DRB1 ∗ 07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups.
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MICB polymorphism in a southern Chinese Han population: the identification of two new MICB alleles, MICB*005:06 and MICB*026.
Human immunology, 2012Co-Authors: Xuexiang Liu, Fenghua Pan, Wei TianAbstract:Abstract In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB ∗ 005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB ∗ 005:06 and MICB ∗ 026, were identified. Aligned with MICB ∗ 005:02, MICB ∗ 005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB ∗ 026 has probably arisen from MICB ∗ 004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A ∗ 02-C ∗ 01-B ∗ 46-MICA ∗ 010-MICB ∗ 005:02-DRB1 ∗ 09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A ∗ 30-C ∗ 06-B ∗ 13:02-MICA ∗ 008:01-MICB ∗ 005:02-DRB1 ∗ 07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups.
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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, 2011Co-Authors: Xuexiang Liu, Wei Tian, Jinhong CaiAbstract:Major histocompatibility complex class I chain-related gene B (MICB) has only been characterized for allelic variation in very few human populations. The MICB polymorphism remains largely unknown in Chinese populations. In this study, 104 healthy unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated by sequence-based typing for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron 1, linkage disequilibrium of MICB with human leukocyte antigen (HLA)-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. Ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01 were the most frequent alleles with frequencies of 51.44, 16.35, and 11.54%, respectively. Significant linkage disequilibrium (LD) was observed for 9 of the 21 HLA-B-MICB haplotypes and 6 of the 17 MICA-MICB haplotypes with a frequency >1.5%. In particular, HLA-B*13:01 and HLA-B*13:02, both of which were frequently represented in this population, exhibited a distinct LD pattern with the MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010 by a single mutation of G to A at position 86 in exon 2, resulting in an amino acid change from arginine to histidine at codon 6. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010 was the most common haplotype, with a frequency of 8.64% in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N demonstrated a frequency of 2.4% in this population. Our results provide for the first time data regarding the MICB genetic polymorphism in northern Chinese Han populations and will form the basis for future studies of the potential role of MICB in allogeneic organ transplantation and disease association in related ethnic groups.
Xuexiang Liu - One of the best experts on this subject based on the ideXlab platform.
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mica MICB polymorphisms and linkage disequilibrium with hla b in a chinese mongolian population
Scandinavian Journal of Immunology, 2016Co-Authors: W Y Wang, Wei Tian, Xuexiang Liu, F M Zhu, Fan WangAbstract:In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008 (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008 (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA-B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLA-linked disease association in populations of related ancestry.
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MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population.
Scandinavian journal of immunology, 2016Co-Authors: W Y Wang, Wei Tian, Xuexiang Liu, F M Zhu, Fan WangAbstract:In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P
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MICB polymorphism in a southern chinese han population the identification of two new MICB alleles MICB 005 06 and MICB 026
Human Immunology, 2012Co-Authors: Xuexiang Liu, Fenghua Pan, Wei TianAbstract:Abstract In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB ∗ 005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB ∗ 005:06 and MICB ∗ 026, were identified. Aligned with MICB ∗ 005:02, MICB ∗ 005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB ∗ 026 has probably arisen from MICB ∗ 004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A ∗ 02-C ∗ 01-B ∗ 46-MICA ∗ 010-MICB ∗ 005:02-DRB1 ∗ 09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A ∗ 30-C ∗ 06-B ∗ 13:02-MICA ∗ 008:01-MICB ∗ 005:02-DRB1 ∗ 07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups.
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MICB polymorphism in a southern Chinese Han population: the identification of two new MICB alleles, MICB*005:06 and MICB*026.
Human immunology, 2012Co-Authors: Xuexiang Liu, Fenghua Pan, Wei TianAbstract:Abstract In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB ∗ 005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB ∗ 005:06 and MICB ∗ 026, were identified. Aligned with MICB ∗ 005:02, MICB ∗ 005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB ∗ 026 has probably arisen from MICB ∗ 004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A ∗ 02-C ∗ 01-B ∗ 46-MICA ∗ 010-MICB ∗ 005:02-DRB1 ∗ 09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A ∗ 30-C ∗ 06-B ∗ 13:02-MICA ∗ 008:01-MICB ∗ 005:02-DRB1 ∗ 07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups.
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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, 2011Co-Authors: Xuexiang Liu, Wei Tian, Jinhong CaiAbstract:Major histocompatibility complex class I chain-related gene B (MICB) has only been characterized for allelic variation in very few human populations. The MICB polymorphism remains largely unknown in Chinese populations. In this study, 104 healthy unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated by sequence-based typing for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron 1, linkage disequilibrium of MICB with human leukocyte antigen (HLA)-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. Ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01 were the most frequent alleles with frequencies of 51.44, 16.35, and 11.54%, respectively. Significant linkage disequilibrium (LD) was observed for 9 of the 21 HLA-B-MICB haplotypes and 6 of the 17 MICA-MICB haplotypes with a frequency >1.5%. In particular, HLA-B*13:01 and HLA-B*13:02, both of which were frequently represented in this population, exhibited a distinct LD pattern with the MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010 by a single mutation of G to A at position 86 in exon 2, resulting in an amino acid change from arginine to histidine at codon 6. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010 was the most common haplotype, with a frequency of 8.64% in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N demonstrated a frequency of 2.4% in this population. Our results provide for the first time data regarding the MICB genetic polymorphism in northern Chinese Han populations and will form the basis for future studies of the potential role of MICB in allogeneic organ transplantation and disease association in related ethnic groups.