• 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.

• 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.

• 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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• 제13권3호
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• pp.86-93
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• 2013

In the present study, we investigated if priming of autoreactive $CD8^+T$ cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of $K^b$-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for $K^b$ binding inhibited IFN-${\gamma}$production and proliferation of TRP2-180-specific $CD8^+T$ cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific $CD8^+T$ cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive $CD8^+T$ cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific $CD8^+T$ cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

• 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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• 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.

• Asian-Australasian Journal of Animal Sciences
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• 제29권3호
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• pp.321-326
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• 2016

The porcine major histocompatibility complex (MHC) is called swine leukocyte antigen (SLA), which controls immune responses and transplantation reactions. The SLA is mapped on pig chromosome 7 (SSC7) near the centromere. In this study, 3 class I (SLA-1, SLA-3, and SLA-2) and 3 class II (DRB1, DQB1, and DQA) genes were used for investigation of SLA haplotypes in Yucatan miniature pigs in Korea. This pig breed is a well-known model organism for biomedical research worldwide. The current study indicated that Korean Yucatan pig population had 3 Class I haplotypes (Lr-4.0, Lr-6.0, and Lr-25.0) and 3 class II haplotypes (Lr-0.5, Lr-0.7, and Lr-0.25). The combinations of SLA class I and II haplotype together, 2 homozygous (Lr-4.5/4.5 and Lr-6.7/6.7) and 3 heterozygous (Lr-4.5/6.7, Lr-4.5/25.25, and Lr-6.7/25.25) haplotypes were identified, including previously unidentified new heterozygous haplotypes (Lr-4.5/4.7). In addition, a new SLA allele typing method using Agilent 2100 bioanalyzer was developed that permitted more rapid identification of SLA haplotypes. These results will facilitate the breeding of SLA homozygous Yucatan pigs and will expedite the possible use of these pigs for the biomedical research, especially xenotransplantation research.

• Asian-Australasian Journal of Animal Sciences
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• 제21권1호
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• pp.35-41
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• 2008

This study was undertaken to investigate the distribution of major histocompatibility complex class II positive (MHC II+) (HLA-DP-like) cells in the cow uterus (cervix, corpus and cornu uteri) and to compare these cells between the estrus and diestrus phases of the estrous cycle. Twenty-nine multiparous cows were used. Tissue samples from the middle of the cervix, the corpus and the right cornu were taken immediately after slaughter at the estrus or diestrus phase. Streptavidin-biotin peroxidase complex staining was used to detect MHC II+ cells. The number of MHC II+ cells per unit area of tissue was counted using image analysis software under a light microscope. Numerous MHC II+ cells were found in the endometrium (cervix, corpus and cornu uteri) in both estrus and diestrus. MHC II+ cells were found in the surface epithelium of the cervix uteri in diestrus, but in the corpus uteri in both estrus and diestrus and in the cornu uteri in estrus. MHC II+ cells were also found freely in the lumen of the glands and between the gland epithelia of the corpus and cornu uteri in both estrus and diestrus. There were also MHC II+ cells in the connective tissue of the myometrium and perimetrium (outside the endometrium) and around the blood vessels. Endothelial cells were frequently positive for MHC II staining. More MHC II+ cells were found in the endometrium than outside the endometrium in both estrus and diestrus (p<0.001). However, there was no difference in the numbers of positive cells between estrus and diestrus either in the endometrium or outside it. These results are the first evidence for HLA-DP-like MHC II+ cells in the bovine uterus. They indicate that antigen presentation by HLA-DP-like MHC II+ cells of the uterus is not influenced by hormonal status.

• Molecules and Cells
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• 제24권1호
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.