• Title/Summary/Keyword: MHC class I

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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.

Lectins Isolated from Mushroom Fomitella fraxinea Enhance MHC-restricted Exogenous Antigen Presentation

  • Kim, Hyun-Jin;Cho, Kyung-Mi;Gerelchuluun, Turmunkh;Lee, Ji-Seon;Chung, Kyeong-Soo;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • v.7 no.4
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    • pp.197-202
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    • 2007
  • Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

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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Immunomodulatory Effects of Hypocrellin A on MHC-restricted Antigen Processing

  • Park, Sun-Im;Im, Sun-A;Kim, Ki-Hyang;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.412-415
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    • 2011
  • Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the $H-2K^b$-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

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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Major histocompatibility complex genes exhibit a potential immunological role in mixed Eimeria-infected broiler cecum analyzed using RNA sequencing

  • Minjun Kim;Thisarani Kalhari Ediriweera;Eunjin Cho;Yoonji Chung;Prabuddha Manjula;Myunghwan Yu;John Kariuki Macharia;Seonju Nam;Jun Heon Lee
    • 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.

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

  • Oh, Byung-Kwon;Hwang, Chan-Seung;Hong, Young-Ho;Kim, Hoon;Kim, Chun-Gil;Min, Hun-Ki
    • Korean Journal of Bronchoesophagology
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    • v.3 no.1
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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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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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    • v.16 no.4
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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.

Tmp21, a novel MHC-I interacting protein, preferentially binds to β2-microglobulin-free MHC-I heavy chains

  • Jun, Young-Soo;Ahn, Kwang-Seog
    • 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.

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

  • Kim, Jin-Ung;Jung, Sung-Ju
    • Journal of fish pathology
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    • v.27 no.1
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    • pp.1-9
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    • 2014
  • The olive flounder, Paralichthys olivaceus is susceptible to viral hemorrhagic septicaemia virus (VHSV) at $15^{\circ}C$ but no mortality at $20^{\circ}C$ even though the virus can grow well in vitro at $20^{\circ}C$. Thus, we designed an experiment to know immune response of olive flounder against VHSV when the host reared at $15^{\circ}C$ or $20^{\circ}C$. cDNA microarray analysis was performed to compare the gene expression patterns of the kidney cells between the host reared at $15^{\circ}C$ or $20^{\circ}C$. The expression of MHC class I, IL-8, myeloperoxidae and endonuclease G-like having function for the antigen presentation and chemokine-factor were up-regulted both the $15^{\circ}C$ and $20^{\circ}C$ during VHSV infection. MHC class II gene existing on antigen-presenting cells and B cell lymphocytes, immunoglobulin (Ig) genes and phagocytosis related genes were down-regulated at $15^{\circ}C$ but highly expressed at $20^{\circ}C$. It can be thought that innate immune related antigen presentation by MHC class I and phagocytosis reaction against VHSV are efficiently occur both the temperature but macrophage or B cell related antigen presentation via MHC class II fails to induce downstream immune reactions (adaptive immunity) to make antibody, and it can be one of the reason that causes high mortality only at $15^{\circ}C$.