• Title/Summary/Keyword: MHC

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Different Way of LMP/TAP/MHC Gene Clustering in Vertebrates,. Viviparity and Anti-tumor Immunity Failure

  • Bubanovic, Ivan;Najman, Stevo
    • 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.

Antigenicity of Fetal Calf Serum as Preserving Solution for Aortic Allograft (동종동맥판 보존용액중 우혈청의 항원효과에 관한 연구)

  • 임창영
    • Journal of Chest Surgery
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    • v.29 no.12
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    • pp.1293-1298
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    • 1996
  • A series of animal experiments has been carried out to investigate the potential antigenicity of the FCS (Fetal Calf Serum) which is commonly used to enhance viability of preserved aortic allograft. Aorti allografts were processed using nutrient media without FCS(control group) or with 10% FCS(study group). After 14 days of 4$^{\circ}C$ cold storage and cryopreservation, antigenic expression of allograft rondothelial cells were studied using immunohistochemical study. To determine antigenicity, level of Anti-MHC class I Antibody, anti-MHC class II antibody and anti-lCAM 1 antibody were measured. There were no stAtistically significant differences in all antigenic expression between control group and study group(p=0. 524 in MHC class I expression, p=0.897 In MHC class II expression, p=0.1305 in ICAM 1 expression). With this result, antigenicity provoking effect of FCS could not be proven. Thus, FCS may not be eliminated from the nutrient media for preservation of aortic allograft due to its proven benefit of cell viability enhancement.

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Oxidized LDL induces phosphorylation of non-muscle myosin IIA heavy chain in macrophages

  • Park, Young Mi
    • 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.

The Effects of Yukmijihwang-tang, Taeksa-tang, Silbi-um on Mesangial cell Proliferation, Fibronectin Synthesis, MHC-class II Expression (육미지황탕(六味地黃湯),택사탕(澤瀉湯), 실비음(實脾飮)이 메산지움세포 증식, Fibronectin 합성 및 MHC-class II 발현에 미치는 영향(影響))

  • Ahn, Sae-Young;Doo, Ho-Kyung;Lee, Jin-Sin
    • The Journal of Internal Korean Medicine
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    • v.21 no.3
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    • pp.433-441
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    • 2000
  • Objective : To analyze the effects of Yukmijihwang-tang, Taeksa-tang, Silbi-um on mesangial cell proliferation, fibronectin synthesis and MHC-class II expression. Methods : Laboratory studies were performed with the method of surface enzyme immunoassays or flow cytometry after addition of peripheral blood mononuclear cells(PBMC) supernatants treated with medications using the cultured human mesangial cells. Results : 1. Silbi-um produces more suppressive effect than control group and hydrocortisone group on the mesangial cell proliferation. In Yukmijihwang-tang, Taeksa-tang and Silbi-um, mesangial cell proliferation significantly decreased than in hydrocortisone group 2. In the 'without fetal bovine serum' study, Yukmijihwang-tang take more suppressive effect than Control group on the fibronectin synthesis. In the 'with fetal bovine serum' study, Yukmijihwang-tang, Taeksa-tang, Silbi-um all have suppressive effect, but it hasn' t any statistical significance. 3. Yukmijihwang-tang, Taeksa-tang, Silbi-um all have a suppressive effect on the MHC-class II expression. Conclusions : Herb medicine generally show a suppressive effect on the suppression of the mesangial cell proliferation, fibronectin synthesis and MHC-class II expression.

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Effects of Sipyukmiyukieum on DNA Synthesis, cAMP Synthesis and MHC-class II Expression of FRTL-5 Thyroid Cells (십육미류기음(十六味流氣飮)이 FRTL-5 갑상선 세포의 DNA와 cAMP의 합성 및 MHC-class II의 발현에 미치는 영향)

  • Kim, Byoung-Woo;Yi, Jae-Eun
    • The Journal of Internal Korean Medicine
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    • v.26 no.2
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    • pp.398-408
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    • 2005
  • Objective: Graves' disease encompasses hyperthyroidism and diffused goiter associated with auto-antibodies to the thyroid stimulating hormone(TSH) receptors. In clinical environment, treatments of Graves' disease have many side effects such as recurrence and hypothyroidism. We've studied the effects of Sipyukmiyukieum on DNA synthesis, cAMP synthesis, and MHC-class II expression of FRTL-5 thyroid cells were studied. Methods: DNA synthesis was investigated by using BrdU staining and cAMP synthesis by ELISA kit, and expression of $interferon-{\gamma}$ activated MHC class II by Flow cytometer. Results: After introduction of Sipyukmiyukieum, significant inhibition of DNA synthesis. cAMP synthesis, and expression of $interferon-{\gamma}$ activated MHC class II of FRTL-5 thyroid cells was observed. Conclusions: Judging from these results, Sipyukmiyukieum has potential as a potent herbal treatment for inhibiting the enlargement of goiter, synthesis of abnormal thyroidal hormones, and autoimmuine responses of Graves' disease.

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Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs

  • Shin, Seulmee;Hyun, Bobae;Lee, Aeri;Kong, Hyunseok;Han, Shinha;Lee, Chong-Kil;Ha, Nam-Joo;Kim, Kyungjae
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.35-41
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    • 2013
  • Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

Genotype Analysis of the Major Histocompatibility Complex Region in Korean Native Chicken (한국 재래닭의 MHC 영역 유전자형 분석)

  • Jung, Kie-Chul;Hoque, Md. Rashedul;Seo, Dong-Won;Park, Byung-Kwon;Choi, Kang-Duk;Lee, Jun-Heon
    • Korean Journal of Poultry Science
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    • v.36 no.4
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    • pp.317-322
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    • 2009
  • The chicken major histocompatibility complex (MHC) is known to be associated with disease resistance and susceptibility to several pathogens. The microsatellite marker LEI0258 is physically located between the BG and BF of MHC region and variations near this marker have been well documented. In this report, the LEI0258 marker was used to find specific alleles for the Korean native chicken. The MHC haplotype was analyzed by PCR screening and sequencing of LEI0258 region in four different breeds including black Korean native chicken, brown Korean native chicken, Cornish and Rhode island red. The serologically same MHC haplotypes showed the differences in repeat numbers, a few indels or single nucleotide polymorphisms by sequencing analysis. Even though we could not identify specific alleles for Korean native chickens, the genotypes analyzed in these breeds can give valuable information for the relationships with disease resistance and establishment of breeding strategies for the Korean native chicken.

Monitoring conservation effects on a Chinese indigenous chicken breed using major histocompatibility complex B-G gene and DNA Barcodes

  • Tu, Yunjie;Shu, Jingting;Ji, Gaige;Zhang, Ming;Zou, Jianmin
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.10
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    • pp.1558-1564
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    • 2018
  • Objective: We report monitoring conservation effect for a Chinese indigenous chicken (Langshan) breed using major histocompatibility complex (MHC) and DNA barcords. Methods: The full length of MHC B-G gene and mitochondrial cytochrome oxidase I (COI) gene in generations 0, 5, 10, 15, 16, and 17 was measured using re-sequencing and sequencing procedures, respectively. Results: There were 292 single nucleotide polymorphisms of MHC B-G gene identified in six generations. Heterozygosity (He) and polymorphic information content (PIC) of MHC B-G gene in generations 10, 15, 16, and 17 remained stable. He and PIC of MHC B-G gene were different in six generations, with G10, G15, G16, G17 >G5>G0 (p<0.05). For the COI gene, there were five haplotypes in generations 0, 5, 10, 15, 16, and 17. Where Hap2 and Hap4 were the shared haplotypes, 164 individuals shared Hap2 haplotypes, while Hap1 and Hap3 were the shared haplotypes in generations 0 and 5 and Hap5 was a shared haplotype in generations 10, 15, 16, and 17. The sequence of COI gene in 6 generations was tested by Tajima's and D value, and the results were not significant, which were consistent with neutral mutation. There were no differences in generations 10, 15, 16, and 17for measured phenotypic traits. In other generations, for annual egg production, with G5, G10, G15, G16, G17>G0 (p<0.05). For age at the first egg and age at sexual maturity, with G10, G15, G16, G17>G5>G0 (p<0.05). Conclusion: Combined with the results of COI gene DNA barcodes, MHC B-G gene, and phenotypic traits we can see that genetic diversity remained stable from generations 10 to 17 and the equimultiple random matching pedigrees conservation population conservation effect of Langshan chicken was effective as measured by these criteria.

Analysis of the Major Histocompatibility Complex Class I Antigen Presentation Machinery in Human Lung Cancer

  • Kim, Hyun-Pyo;Jin, Mi-Rim;Kim, Ick-Young;Ahn, Byung-Yoon;Kang, Seong-Man;Choi, Eui-Ju;Kim, Joon;Kim, Ik-Hwan;Ahn, Kwang-Seog
    • Journal of Microbiology and Biotechnology
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    • v.9 no.3
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    • pp.346-351
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    • 1999
  • Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In order to investigate whether the major histocompatibility complex (MHC) class I-mediated antigen processing machinery is preserved in human lung cancer cell lines, we examined the expression of multiple components of the MHC class I antigen processing pathway, including transporter associated with antigen processing (TAP), $\beta_2$-microglobulin, MHC class I molecules, and chaperones which have not been previously examined in this context. Row cytometry analysis showed that the cell surface expression of MHC class I molecules was downregulated in all of the cell lines. While some cell lines showed no detectable expression of MHC class I molecules, pulse-chase experiments showed that MHC class I molecules were synthesized in the other cell lines but not transported from the endoplasmic reticulum to the cell surface. Low or nondetectable levels of TAP1 and/or TAP2 expression were demonstrated by Western blot analysis in all of the cell lines, representing a variety of lung tissue types. In some cases, this was accompanied by loss of tapasin expression. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. This study provides further information for designing the potential therapeutic applications such as immunotherapy and gene therapy against cancers.

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Potentiation of T Cell Stimulatory Activity by Chemical Fixation of a Weak Peptide-MHC Complex

  • Hwang, Inkyu;Kim, Kwangmi;Choi, Sojin;Lomunova, Maria
    • Molecules and Cells
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    • v.40 no.1
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    • pp.24-36
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    • 2017
  • The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by $L^d$ MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for $L^d$ is measurably weaker than that of QL9, but either peptides in the context of $L^d$ interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, $EC_{50}s$ of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for $L^d$. When $EC_{50}s$ for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, $L^d/P2Ca$ dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of $L^d/P2Ca$ with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.