• BMB Reports
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• v.48 no.1
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• pp.48-53
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• 2015

Oxidized LDL (oxLDL) performs critical roles in atherosclerosis by inducing macrophage foam cell formation and promoting inflammation. There have been reports showing that oxLDL modulates macrophage cytoskeletal functions for oxLDL uptake and trapping, however, the precise mechanism has not been clearly elucidated. Our study examined the effect of oxLDL on non-muscle myosin heavy chain IIA (MHC-IIA) in macrophages. We demonstrated that oxLDL induces phosphorylation of MHC-IIA (Ser1917) in peritoneal macrophages from wild-type mice and THP-1, a human monocytic cell line, but not in macrophages deficient for CD36, a scavenger receptor for oxLDL. Protein kinase C (PKC) inhibitor-treated macrophages did not undergo the oxLDL-induced MHC-IIA phosphorylation. Our immunoprecipitation revealed that oxLDL increased physical association between PKC and MHC-IIA, supporting the role of PKC in this process. We conclude that oxLDL via CD36 induces PKC-mediated MHC-IIA (Ser1917) phosphorylation and this may affect oxLDL-induced functions of macrophages involved in atherosclerosis.

• BMB Reports
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• v.44 no.6
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• pp.369-374
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• 2011

MHC-I molecules play a critical role in immune surveillance against viruses by presenting peptides to cytotoxic T lymphocytes. Although the mechanisms by which MHC-I molecules assemble and acquire peptides in the ER are well characterized, how MHC-I molecules traffic to the cell surface remains poorly understood. To identify novel proteins that regulate the intracellular transport of MHC-I molecules, MHC-I-interacting proteins were isolated by affinity purification, and their identity was determined by mass spectrometry. Among the identified MHC-I-associated proteins was Tmp21, the human ortholog of yeast Emp24p, which mediates the ER-Golgi trafficking of a subset of proteins. Here, we show that Tmp21 binds to human classical and non-classical MHC-I molecules. The Tmp21-MHC-I complex lacks ${\beta}_2$-microglobulin, and the number of the complexes is increased when free MHC-I heavy chains are more abundant. Taken together, these results suggest that Tmp21 is a novel protein that preferentially binds to ${\beta}_2$-microglobulin-free MHC-I heavy chains.

• Animal cells and systems
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• v.9 no.1
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• pp.1-7
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• 2005

Class I and class II MHC genes have been identified in most of the jawed vertebrate taxa. In all investigated bony fish species, unlike mammals, the classical class I and class II MHC genes are not linked and even are found on different chromosomes. Linking and clustering of the class I and class II MHC genes is not the only phenomenon clearly detected in the evolution of immune system from cartilaginous to mammals. In all non-mammalian classes the LMP/TAP genes are highly conserved within class I genes region, while these genes are conserved within class II genes region only in mammals. Today we know that LMP/TAP genes in mammals have a crucial role in peptide processing for presentation within class I molecules, as well as in anti-tumor immunity. For these reasons, differences in clustering of LMP/TAP/MHC genes can be responsible for the differences in mechanisms and efficacy of anti-tumor immunity in non-mammalian vertebrates compared to same mechanisms in mammals. Also, the differences in cytokine network and anti-tumor antigens presentation within classes of vertebrates can be explained by toe peculiarity of LMP/TAP/MHC gene clustering.

• Animal Bioscience
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• v.37 no.6
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• pp.993-1000
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• 2024

Objective: This study was conducted to investigate the differential expression of the major histocompatibility complex (MHC) gene region in Eimeria-infected broiler. Methods: We profiled gene expression of Eimeria-infected and uninfected ceca of broilers sampled at 4, 7, and 21 days post-infection (dpi) using RNA sequencing. Differentially expressed genes (DEGs) between two sample groups were identified at each time point. DEGs located on chicken chromosome 16 were used for further analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was conducted for the functional annotation of DEGs. Results: Fourteen significant (false discovery rate <0.1) DEGs were identified at 4 and 7 dpi and categorized into three groups: MHC-Y class I genes, MHC-B region genes, and non-MHC genes. In Eimeria-infected broilers, MHC-Y class I genes were upregulated at 4 dpi but downregulated at 7 dpi. This result implies that MHC-Y class I genes initially activated an immune response, which was then suppressed by Eimeria. Of the MHC-B region genes, the DMB1 gene was upregulated, and TAP-related genes significantly implemented antigen processing for MHC class I at 4 dpi, which was supported by KEGG pathway analysis. Conclusion: This study is the first to investigate MHC gene responses to coccidia infection in chickens using RNA sequencing. MHC-B and MHC-Y genes showed their immune responses in reaction to Eimeria infection. These findings are valuable for understanding chicken MHC gene function.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.287-299
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• 1994

Plasma protein which has been known as one of nonspecific immunostimulators was added to feedstuff to examine its effect on the enhancement of cellular immune response in porcine immune system. A total of 40 piglets, 20 male and 20 female each, were fed for 30 days with or without plasma protein. The peripheral blood were collected and analyzed for the investigation of leukocyte subpopulations and their activities by using a panel of monoclonal antibodies specific to porcine leukocyte differentiation antigens and flow cytometry. The results obtained as follows. 1. Subpopulations expressing major histocompatibility complex(MHC) class I antigen were $96.2{\pm}3.1%$ and $86.6{\pm}3.8%$ in piglets fed with plasma protein and in piglets fed without plasma protein, respectively. 2. Proportion of leukocyte subpopulation expressing MHC class II antigens were significantly higher in the piglets fed with plasma protein than ones without plasma protein. The proportion was $27.6{\pm}3.6%$ and $16.6{\pm}2.2%$ in MHC class II DQ antigen, and $28.1{\pm}2.0%$ and $20.0{\pm}0.3%$ in MHC class II DR antigen, respectively. 3. A significant increase in the proportion of cells expressing poCD2 was not found in piglets fed plasma protein. 4. Proportion of subpopulation expressed porcine(Po) CD4 antigens which specific to helper T lymphocytes were not increased (18.3-19.1% vs. 25.6-28.8%), rather slightly decreased, in plasma protein-treated group. 5. The most important increase of proportion in plasma protein-treated group was the leukocyte subpopulation specific to $poCD8^+$ T cytotoxic/suppressor lymphocytes. The expression level was significantly higher up to 45.9-47.1% in plasma protein-treated group in comparing with 29.7-33.0% in non-plasma protein-treated group. 6. Lymphoblastogenetic responses using different concentrations of Con A mitogen and plasma protein has found that the responses of lymphocyte from piglets fed plasma protein was significantly activated (p<0.01). The activities measured by 3[H]-thymidine incorporation showed 3-6 times stronger in plasma protein-treated group than those in non-plasma protein-treated group. The study has concluded that plasma protein, which has known as a nonspecific immunostimulator, may have an immunoenhancing activities in porcine lymphoid system by increase the activated cell proportions and their blastogenetic properties which is critical to host immune responses.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.138-146
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• 2009

Background: The MHC region of the chromosome contains a lot of genes involved in immune responses. Here we have investigated the mouse NG29/Cd320 gene in the centrometrically extended MHC region of chromosome 17. Methods: We cloned the NG29 gene by RT-PCR and confirmed the tissue distribution of its gene expression by northern blot hybridization. We generated the NG29 gene expression constructs and polyclonal antibody against the NG29 protein to perform the immunofluorescence, immunoprecipitation and flow cytometric analysis. Results: The murine NG29 gene and its human homologue, the CD320/8D6 gene, were similar in the gene structure and tissue expression patterns. We cloned the NG29 gene and confirmed its expression in plasma membrane and intracellular compartments by transfecting its expresssion constructs into HEK 293T cells. The immunoprecipitation studies with rabbit polyclonal antibody raised against the NG29-NusA fusion protein indicated that NG29 protein was a glycoprotein of about 45 kDa size. A flow cytometric analysis also showed the NG29 expression on the surface of Raw 264.7 macrophage cell line. Conclusion: These findings suggested that NG29 gene in mouse extended MHC class II region was the orthologue of human CD320 gene even though human CD320/8D6 gene was located in non-MHC region, chromosome 19p13.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.10
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• pp.1359-1365
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• 2009

We performed a genome-wide linkage and quantitative trait locus (QTL) analysis to confirm the existence of QTL affecting Rous Sarcoma Virus (RSV) induced tumor regression, and to estimate their effects on phenotypic variance in an F2 resource population. The F2 population comprised 158 chickens obtained by crossing tumor regressive White Leghorn (WL) and tumor progressive Rhode Island Red (RIR) lines was measured for tumor formation after RSV inoculation. Forty-three tumor progressive and 28 tumor regressive chickens were then used for genome-wide linkage and QTL analysis using a total of 186 microsatellite markers. Microsatellite markers were mapped on 20 autosomal chromosomes. A significant QTL was detected with marker LEI0258 located within the MHC B region on chromosome 16. This QTL had the highest F ratio (9.8) and accounted for 20.1% of the phenotypic variation. Suggestive QTL were also detected on chromosomes 4, 7 and 10. The QTL on chromosome 4 were detected at the 1% chromosome-wide level explaining 17.5% of the phenotypic variation, and the QTLs on chromosome 7 and 10 were detected at the 5% chromosome-wide level and explained 11.1% and 10.5% of the phenotypic variation, respectively. These results indicate that the QTLs in the non-MHC regions play a significant role in RSV-induced tumor regression. The present study constitutes one of the first preliminary reports in domestic chickens for QTLs affecting RSV-induced tumor regression outside the MHC region.

• Genomics & Informatics
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• v.15 no.2
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• pp.65-68
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• 2017

Ankylosing spondylitis (AS) is a chronic autoinflammatory disease that affects the spine and sacroiliac joints. Regarding its etiology, although HLA-B27 is known to be the strongest genetic factor of AS, much evidence suggests the potential contribution of non-MHC genes to the susceptibility to AS. Most of these non-MHC genes have been discovered in non-Asian populations; however, just some of them have been validated in Koreans. In this study, we aimed to identify additional AS-associated single-nucleotide polymorphism (SNP) candidates by replicating the candidate SNPs in Korean AS patients and healthy controls. For this, we selected three SNPs (rs11249215 in RUNX3, rs6556416 in IL12B, and rs8070463 in TBKBP1), which were previously reported as risk factors of AS but have not been studied in Koreans, and performed genotyping assays using a total of 1138 Korean samples (572 AS patients and 566 healthy controls). Of the three SNP candidates, one SNP in RUNX3 (rs11249215) was significantly associated with the risk of AS (odds ratio, 1.31; 95% confidence interval, 1.02 to 1.68, p = 0.03). These results will be helpful in elucidating the pathogenesis of AS and may be useful for developing AS risk prediction models in Koreans.

• Journal of the Korean Institute of Intelligent Systems
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• v.13 no.1
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• pp.119-124
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• 2003

In this paper, we modeled positive selection and negative selection that is developing process of cytotoxic T-cell that plays important role in biological immune system. Also, we developed change detection algorithm, which is very Important part in detecting data change by intrusion and data infection by computer virus. Proposed method is the algorithm that produces MHC receptor lot recognizing self and antigen detector for recognizing non-self. Therefore, proposed method detects self and intruder by two type of detectors like real immune system. We show the effectiveness and characteristics of proposed change detection algorithm by simulation about point and block change of self file.

• Molecules and Cells
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• v.24 no.1
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.