• Animal cells and systems
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• 제9권1호
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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.

• IMMUNE NETWORK
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• 제7권4호
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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.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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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.

• IMMUNE NETWORK
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• 제11권6호
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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.

• Journal of Chest Surgery
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• 제29권12호
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• pp.1293-1298
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• 1996

동종동맥판의 보존용액에 흔히 첨가되는 우혈청(Fetal Calrserum)의 항원성을 검사하기 위하여 쥐를 이용한 실험을 하였다 동종동맥 판을 2개의 군으로 나누어 대조군은 우릴청을 첨가하지 않은 보존용액을 사용하여 보존처리하고, 실험군은 우혈청을 첨가한 보존용액을 사용하여 보존처리하였다. 14일간에 걸친 냉장보존(4$^{\circ}C$) 및 냉동보존후 혈관내피세포를 분리하여 면역화학적 검사를 통한 면역표현정도를 조사하였다. 이때 면역표현정도의 검사로써 MHC class I 항체, MHC class II항체, ICAM-1 항체를 측정하였다. 실험의 결과 대조군과 실험군사이에 통계적으로 의미있는 차이를 발견할 수 없었다(MHC class I 표현: p=0.524, MHC class 표현: p=0.897, ICAM 1 표현: p=0.1305). 이와 같은 결과를 볼 때 동종동맥판의 보존처리를 할 때 세포의 생육성보존효과를 갖고있는 우혈청을 보존용액에서 배제하는 것이 바람직하다고 볼 수 없다.

• Animal Bioscience
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• 제37권6호
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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.

• 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.

• 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-K^b 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.

• BMB Reports
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• 제44권6호
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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.

• 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.