• Title/Summary/Keyword: HLA-DRA

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Replicated Association Study between Tuberculosis and CLCN6, DOK7, HLA-DRA in Korean

  • Kim, Sung-Soo;Park, Min;Park, Sangjung
    • Biomedical Science Letters
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    • v.26 no.3
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    • pp.238-243
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    • 2020
  • Tuberculosis is a global public health problem and manifests itself as a difference in the genetic susceptibility of the host, along with the properties of Mycobacterium tuberculosis (MTB). The single nucleotide polymorphisms (SNPs) and candidate genes proposed in the Genome-wide association study (GWAS) on tuberculosis in a recently published Chinese population were reported. In this study, we investigated whether the genetic polymorphism of candidate genes related to tuberculosis is reproduced when targeting Koreans. The CLCN6 (rs12404124, rs198391, rs535107), DOK7 (rs1203104, rs1203103) and HLA-DRA (rs1051336) gene polymorphisms showed statistically significant results. In addition, it was also found whether it acts as an expression quantitative trait loci (eQTL) that can influence gene expression. This study confirmed that the genetic polymorphism of the three genes (CLCN6, DOK7, HLA-DRA) affects the development of tuberculosis and will help to understand the genetic specificity of tuberculosis and the interaction between pathogens and hosts.

Korean BAC Library Construction and Characterization of HLA-DRA, HLA-DRB3

  • Park, Mi-Hyun;Lee, Hye-Ja;Bok, Jeong;Kim, Cheol-Hwan;Hong, Seong-Tshool;Park, Chan;Kimm, Ku-Chan;Oh, Berm-Seok;Lee, Jong-Young
    • BMB Reports
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    • v.39 no.4
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    • pp.418-425
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    • 2006
  • A human bacterial artificial chromosome (BAC) library was constructed with high molecular weight DNA extracted from the blood of a male Korean. This Korean BAC library contains 100,224 clones of insert size ranging from 70 to 150 kb, with an average size of 86 kb, corresponding to a 2.9-fold redundancy of the genome. The average insert size was determined from 288 randomly selected BAC clones that were well distributed among all the chromosomes. We developed a pooling system and three-step PCR screen for the Korean BAC library to isolate desired BAC clones, and we confirmed its utility using primer pairs designed for one of the clones. The Korean BAC library and screening pools will allow PCR-based screening of the Korean genome for any gene of interest. We also determined the allele types of HLA-DRA and HLA-DRB3 of clone KB55453, located in the HLA class II region on chromosome 6p21.3. The HLA-DRA and DRB3 genes in this clone were identified as the DRA*010202 and DRB3*01010201 types, respectively. The haplotype found in this library will provide useful information in future human disease studies.

Enhancement of immunomodulatory activity by liposome-encapsulated natural phosphodiester bond CpG-DNA in a human B cell line

  • Kim, Dong-Bum;Rhee, Jae-Won;Kwon, Sang-Hoon;Kim, Young-Eun;Choi, Soo-Young;Park, Jin-Seu;Lee, Young-Hee;Kwon, Hyung-Joo
    • BMB Reports
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    • v.43 no.4
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    • pp.250-256
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    • 2010
  • Natural phosphodiester bond CpG-DNA that contains immunomodulatory CpG motifs (PO-DNA) upregulates the expression of proinflammatory cytokines and induces an Ag-driven Th1 response in a CG sequence-dependent manner in mice. In humans, only phosphorothioate backbone-modified CpG-DNA (PS-DNA) and not PO-DNA has immunomodulatory activity. In this study, we found that liposome-encapsulated PO-DNA upregulated the expression of human $\beta$-defensin-2 (hBD-2) and major histocompatibility class II molecules (HLA-DRA) in a CG sequence-dependent and liposome- dependent manner in human B cells. Of the three different liposomes, DOTAP has the unique ability to enhance the immunomodulatory activity of PO-DNA. In contrast, HLA-DRA and hBD-2 promoter activation can be induced by liposome-encapsulated PS-DNA in a CG sequence-independent manner, depending on the CpG-DNA species. Our observations demonstrate that, when encapsulated with a proper liposome in the immune system, natural PO-DNA has the potential to be a useful therapy for the regulation of the innate immune response.

The production and immunostimulatory activity of double-stranded CpG-DNA

  • Park, Byoung-Kwon;Kim, Dong-Bum;Rhee, Jae-Won;Kim, Min-Soo;Seok, Hyun-Jeong;Choi, Soo-Young;Park, Jin-Seu;Lee, Young-Hee;Kwon, Hyung-Joo
    • BMB Reports
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    • v.43 no.3
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    • pp.164-169
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    • 2010
  • CpG-DNA, which contains unmethylated CpG dinucleotides in the context of specific sequences, has remarkable and diverse immunological effects, including induction of proinflammatory cytokine expression and regulation of the Th1/Th2 immune response. Here, we examined the immunostimulatory activities of double-stranded (ds) CpG-DNA in the human B cell line RPMI8226. To investigate whether dsCpG-DNA stimulates immune cells, we constructed a plasmid containing repeated dsCpG-DNA and produced dsCpG-DNA by PCR amplification and EcoR I digestion. PCR-amplified dsCpG-DNA alone did not have immmunostimulatory activity. However, dsCpGDNA encapsulated with lipofectin induced IL-8 promoter activation, HLA-DRA expression, and IL-8 expression in a CG sequence-independent manner. The effects of encapsulated dsCpGDNA were independent of minor endotoxin contamination. These findings suggest the potential use of dsCpG-DNA as a therapy for immune response regulation.