• 제목/요약/키워드: MHC

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Two Sjogren syndrome-associated oral bacteria, Prevotella melaninogenica and Rothia mucilaginosa, induce the upregulation of major histocompatibility complex class I and hypoxia-associated cell death, respectively, in human salivary gland cells

  • Lee, Jaewon;Jeon, Sumin;Choi, Youngnim
    • International Journal of Oral Biology
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    • 제46권4호
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    • pp.190-199
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    • 2021
  • Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.

바이러스성 출혈성 패혈증에 감염된 넙치의 cDNA microarray 분석 : 수온에 따른 면역 유전자 발현의 차이 (cDNA microarray analysis of viral hemorrhagic septicemia infected olive flounder, Paralichthys olivaceus: immune gene expression at different water temperature)

  • 김진웅;정성주
    • 한국어병학회지
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    • 제27권1호
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    • pp.1-9
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    • 2014
  • 저수온기만 넙치에 대량 폐사를 일으키는 바이러스성 출혈성 패혈증을 폐사가 발생하는 $15^{\circ}C$, 폐사가 발생하지 않는 $20^{\circ}C$에서 인공감염시켜 넙치의 면역 유전자 발현 profile을 cDNA microarray 분석하였으며, 특히 저수온기에 폐사가 나타나는 원인을 면역 유전자 발현과 관련시켜 알아보고자 하였다. $15^{\circ}C$, $20^{\circ}C$의 감염 세포구에 공통으로 발현되는 유전자는 MHC class I, IL-8, myeloperoxidase 및 endonuclease G-like 유전자로 모든 세포표면에 존재하여 항원을 제시하거나 호중구 주화성을 자극하는 유전자들이었다. 항원 가공 및 제시, 항체 생성에 관여하는 MHC class II, immunoglobulin (Ig)과 retinoblastoma 등의 유전자는 $20^{\circ}C$에서는 발현이 증가하였으나 $15^{\circ}C$에서는 발현이 감소되었다. 이로부터 폐사가 발생하지 않는 $20^{\circ}C$는 바이러스 감염초기의 항원 제시, MHC class I과 II에 의한 항원제시, apoptosis 및 이후의 항체 생산이 정상적으로 이루어져 폐사가 발생하지 않는 것으로 생각되었다. 그러나 폐사가 발생하는 $15^{\circ}C$에서는 MHC class I매개의 항원 제시와 탐식 작용등의 선천 면역은 이루어지나 macrophage에 의한 MHC class II매개의 항원 제시와 apoptosis저하, 항체 생산 관련 유전자의 발현저하가 관찰되어 초기 macrophage에 의한 항원제시의 실패로 적응 면역이 제대로 활성화되지 않아 폐사가 발생한 것으로 사료된다.

후두편평세포암종에서 Human papillomavirus의 검출과 주조직적합복합체(Major Histocompatibility Complex: MHC) Class I 발현양상 (Detection of Human Papillomavirus and Expression of MHC Class I in Laryngeal Squamous Cell Carcinoma)

  • 오병권;황찬승;홍영호;김훈;김춘길;민헌기
    • 대한기관식도과학회지
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    • 제3권1호
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    • pp.70-78
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    • 1997
  • The development of preneoplastic and neoplastic squamous cell proliferations of body sites such as the skin, female lower genital tract, and larynx is strongly associated with specific types of human papillomaviruses (HPV). Antitumor $CD^{8+}$ cells recognize peptide antigens presented on the surface of tumor cells by major histocompatibility complex (MHC) class I molecules. The MHC class I molecule is a heterodimer composed of an integral membrane glycoprotein designated the alpha chain and a noncovalently associated, soluble protein called beta-2-microglobulin( $\beta$ -2-m). Loss of $\beta$-2-m generally eliminates antigen recognition by antitumor $CD^{8+}$ T cells. We evaluated the expression of $\beta$-2-m as a potential means of tumor escape from immune recognition and the presence of HPV DNA as a cause of laryngeal squamous cell carcinomas (SCCs). Laryngeal SCCs (n=39) were analyzed for MHC class I expression by immunohistochemistry and for presence of HPV by in situ hybridization technique. The results were as follows : 1) HPV DNA was detected in 10 (25.64%) out of 39 cases in laryngeal squamous cell carcinomas. 2) MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions. 3) The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement. In conclusion, HPV was thought to be the etiological factor of SCC of larynx, and we found that the down-regulation of MHC class I was a common phenomenon In laryngeal SCC and may provide a way for tumor cells to escape from immune surveillance.

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IMGT Unique Numbering for Standardized Contact Analysis of Immunoglobulin/antigen and T cell receptor/peptide/MHC Complexes

  • Kaas, Quentin;Chiche, Laurent;Lefrane, Marie-Paule
    • 한국생물정보학회:학술대회논문집
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    • 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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    • pp.209-214
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    • 2005
  • Immunoglobulins (IG) , T cell receptors (TR) and major histocompatibility complex (MHC) are major components of the immune system. Their experimentally determined three-dimensional (3D) structures are numerous and their retrieval and comparison is problematic. IMGT, the international ImMunoGeneTics information system$^{\circledR}$(http://imgt.cines.fr), has devised controlled vocabulary and annotation rules for the sequences and 3D structures of the IG TR and MHC. Annotated data from IMGT/3D sructure-DB, the IMGT 3D structure database, are used in this paper to compare 3D structure of the domains and receptor, and to characterize IG/antigen, peptide/MHC and TR/peptide/MHC interfaces. The analysis includes angle measures to assess receptor flexibility, structural superimposition and contact analysis. Up-to-date data and analysis results are available at the IMGT Web site, http://imgt.cines.fr.

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Identification of potential molecular markers for disease resistance in giant gourami through major histocompatibility complex (MHC) II gene analysis

  • Ikhsan Khasani;Rita Febrianti;Sularto;Wahyu Pamungkas;Keukeu Kaniawati Rosada
    • Fisheries and Aquatic Sciences
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    • 제27권3호
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    • pp.159-170
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    • 2024
  • Research to obtain molecular markers related to the major histocompatibility complex (MHC) gene in both strains of gourami is essential to increase the success of the selection program of disease resistance traits. Using a completely randomized design (CRD), the challenge test consists of four treatments and seven replications. The treatment was Jambi gourami injected with PBS (KJ), Kalimantan gourami injected with PBS (KK), Jambi strain injected with Aeromonas hydrophila (GJ), and Kalimantan strain injected with A. hydrophila (GK). The GJ population was more resistant to A. hydrophila than the GK population. The MHC II gene was detected in both test strains (GJ and GK), both resistant and susceptible fish. However, there were differences in the results of amplifying the MHC II gene in susceptible and resistant fish. Two DNA fragments approximately 400 and 585 bp were detected in the genome of susceptible fish, while in the genome of susceptible fish, only one DNA fragment was detected (400 bp). Therefore, the MHC II gene fragment with a size of about 585 bp can be used as a potential candidate for specific molecular markers to obtain resistance to A. hydrophila bacteria in the giant gourami.

Vanilloid Receptor 1 Agonists, Capsaicin and Resiniferatoxin, Enhance MHC Class I-restricted Viral Antigen Presentation in Virus-infected Dendritic Cells

  • Young-Hee Lee;Sun-A Im;Ji-Wan Kim;Chong-Kil Lee
    • IMMUNE NETWORK
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    • 제16권4호
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    • pp.233-241
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    • 2016
  • DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-Kb complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.

발포 폴리스티렌 폼을 이용한 다기능 열선절단장치 개발 (Development of Multi-functional Hotwire Cutting System using EPS-foam)

  • 이상호;김효찬;양동열;박승교;김찬국
    • 한국정밀공학회:학술대회논문집
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    • 한국정밀공학회 2004년도 추계학술대회 논문집
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    • pp.1414-1417
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    • 2004
  • A thick-layered RP process, transfer-type variable lamination manufacturing using expandable polystyrene foam (VLMST) has been developed to have the advantageous characteristics such as high building speed, low cost for introduction and maintenance of VLM-ST apparatus, and little staircase surface irregularities of parts. However, VLM-ST has difficulty fabricating an axisymmetric shape and a large-sized freeform shape because of the limited sloping angles and small build size. The objective of this paper is to develop a multi-functional hotwire cutting system using EPS-foam (MHC). MHC employs a four-axis synchronized hotwire cutter with the structure of two XY movable heads and a turntable. In order to examine the applicability of the developed MHC apparatus, an axisymmetric shape, a polyhedral shape and a large-sized freeform shape were fabricated on the apparatus.

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Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone

  • Im, Sun-A;Gerelchuluun, Turmunkh;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • 제14권6호
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    • pp.328-332
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    • 2014
  • Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.

Characterization of a Novel Gene in the Extended MHC Region of Mouse, NG29/Cd320, a Homolog of the Human CD320

  • Park, Hyo-Jin;Kim, Ji-Yeon;Jung, Kyung-In;Kim, Tae-Jin
    • IMMUNE NETWORK
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    • 제9권4호
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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.

Inhibition of Major Histocompatibility Complex (MHC)-Restricted Presentation of Exogenous Antigen in Dendritic Cells by Korean Propolis Components

  • Han, Shin-Ha;Cho, Kyung-Hae;Lee, Seung-Jeong;Lee, Chong-Kil;Song, Young-Cheon;Ha, Nam-Joo;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • 제5권3호
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    • pp.150-156
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    • 2005
  • Background: Dendritic cells (DCs) playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of antigen presenting cell (APC) function of DCs, we searched for and characterized APC function modulators from natural products. Methods: DCs were cultured in the presence of propolis components, WP and CP, and then examined for their ability to present exogenous antigen in association with major histocompatibility complexes (MHC). Results: WP and CP inhibited class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells, and DCs generated from bone marrow cells with GM-CSF and IL-4. The inhibitory activity of WP and CP appeared to be due not only to inhibition of phagocytic activity of DCs, but also to suppression of expression of MHC molecules on DCs. We also examined the effects of WP and CP on T cells. Interestingly, WP and CP increased IL-2 production from T cells. Conclusion: These results demonstrate that WP and CP inhibit MHC-restricted presentation of exogenous antigen through down-regulation of phagocytic activity and suppression of expression of MHC molecules on DCs.