• Title/Summary/Keyword: Antigen-presenting cell

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A New Artificial Immune System Based on the Principle of Antibody Diversity And Antigen Presenting Cell (Antibody Diversity 원리와 Antigen Presenting Cell을 구현한 새로운 인공 면역 시스템)

  • 이상형;김은태;박민용
    • Journal of the Institute of Electronics Engineers of Korea CI
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    • v.41 no.4
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    • pp.51-58
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    • 2004
  • This paper proposes a new artificial immune approach to on-line hardware test which is the most indispensable technique for fault tolerant hardware. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. In addition, antigen presenting cell (APC) is realized by Quine-McCluskey method in this algorithm and tolerance conditions are generated through GA (Genetic Algorithm). The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

The Prospective of Antigen-presenting Cells in Cancer Immunotherapy (항원제시세포를 이용한 암 치료제 개발전망)

  • Shim Doo-Hee;Lee Jae-Hwa
    • KSBB Journal
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    • v.19 no.6 s.89
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    • pp.415-420
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    • 2004
  • All around the world, the rate of attack of cancer diseases has been going up and the number of cancer patients has been increasing every year. Cancer can be divided into malignant tumor and benign tumor according to its growth appearance. Many studies and experiments have been conducted and the various treatment are being created to find the way to care malignant. Dendritic cells (DCs), which is an agent of cancer treatments by using an immune reaction in our body, plays an important role to present by a tumor antigen to cytotoxic T-cell and help them to attack the tumor cell directly. However there are some defects of this therapy. Soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) based artificial antigen presenting cell (aAPC) as the antigen presenting cell (APC) which is complement and overcome some of the limitations of dendritic cell-based vaccines and ex vivo expansion of human T cells is new method for cancer therapy. In this article, we are reviewing the role of DCs and the treatment with it, and searching for the possibility of the new development of immunotherapy for cancer.

The Cell Surface Expression of H2-M3 Does Not Directly Effect on the Killing Activity of NK Cell (H2-M3의 세포 표면 발현이 NK 세포의 활성에 미치는 영향 분석)

  • Lee, Sang-Yeol;Chun, Tae-Hoon
    • YAKHAK HOEJI
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    • v.53 no.3
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    • pp.125-129
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    • 2009
  • H2-M3 (M3) is a unique antigen presenting molecule which provides N-formylated peptide to certain type of T cells. Previous observation indicated that NK cell activity is significantly diminished during listerial infection in $H2-M3^{-/-}$ mice. To explore the possibility that M3 expression directly effect on NK cell activity, we measured NK cell activity with or without stimulation of N-formylated peptide on antigen presenting cells. Results indicated that the expression of M3 is not directly influence on NK cell activity. Further study will be focused on the indirect effect of M3 on regulating NK cell activity.

The effects of properties and interactions of surface molecules in antigen presenting cells on T cell activation (인공 항원제시세포의 표면 분자의 특성 및 상호작용이 T 세포 활성화에 미치는 영향)

  • Min, Youngsil;Kang, Yoon Joong
    • Journal of Convergence for Information Technology
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    • v.10 no.6
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    • pp.164-176
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    • 2020
  • Efficient production of antigen specific cytotoxic T cells is critical for appropriate adoptive immune response. In vitro culture and expansion of human T lymphocyte clones are very sophisticated and subtle procedure in immune cell therapy and hard to control. Therefore, many groups devoted their efforts to manipulate artificial antigen presenting cells (aAPCs) that can induce T cell activation and clonal expansion. To mimicking of natural antigen-presenting cells, aAPCs encompass basic signal molecules required for T cell activation: MHC:antigen complexes, co-stimulatory molecules and soluble immune modulating molecules. Orchestrated organization of these molecules is important for efficient T cell activation. Here, we discuss how those molecules have been incorporated in several aAPC models, but also how physical properties od aAPC are important for interaction with T cells.

Modulatory Effect of Kaempferitrin, a 3,7-Diglycosylflavone, on the LPS-Mediated Up-regulation of Surface Co-stimulatory Molecules and CD29-Mediated Cell-cell Adhesion in Monocytic- and Macrophage-like Cells (활성화된 단핵구 및 대식세포의 항원제시기능에 대한 Kaempferitrin의 조절 효과)

  • Kim, Byung-Hun;Cho, Dong-Ha;Cho, Jae-Youl
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.482-489
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    • 2007
  • Kaempferitrin, isolated from Kenaf (Hibiscus cannabinus), was examined to evaluate its modulatory effects on antigen-presenting cell functions of macrophages/monocytes such as phagocytosis of foreign materials, up-regulation of costimulatory molecules (CD40, CD80 and CD86), adhesion molecule activation, and antigen processing and presentation. Kaempferitrin strongly blocked up-regulation of CD40, CD80 and CD86, but not pattern recognition receptor (PRR) (e.g., TLR2). It also suppressed functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay, required for T cell-antigen-presenting cell (APC) interaction. Furthermore, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. However, the compound did not diminish phagocytic uptake, an initial step for antigen processing, and ROS generation in RAW264.7 cells. In particular, to understand molecular mechanism of kaempferitrin-mediated inhibition, the regulatory role of LPS-induced signaling events was examined using immunoblotting analysis. Interestingly, this compound dose dependently suppressed the phosphorylation of $I{\kappa}B{\alpha}$, Src, Akt and Syk, demonstrating that it can negatively modulate the activation of these signaling enzymes. Therefore, our data suggested that kaempferitrin may be involved in regulating APC function-relevant immune responses of macrophages and monocytes by regulating intracellular signaling.

Differential Activation of T Cells by T-Cell Receptor Ligand Analogs

  • Choi, Yun-Hi;Suh, Yu-Jin;Kim, Kil-Hyoun
    • BMB Reports
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    • v.30 no.6
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    • pp.415-420
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    • 1997
  • Although $CD4^+$ T cell responses to protein-derived antigen have well been understood, the epitopes recognized by hapten-specific $CD4^+$ T cells have not been fully defined. In this study, we characterized the response of a T cell hybridoma (5Di0.1B8) which is specific for a hapten. N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) restricted by MHC class II $I-A^d$. Using three different antigen presenting cells (APCs) expressing $I-A^d$, the role of class II MHC proteins in haptenic antigen presentation and subsequent activation of 5D10.1B8 has been examined. Activation of 5D10.1B8 T cells by HSAB analogs was also performed. Our results show that each APC activated T cells differentially and that interleukin-2 (IL-2) augmented antigen-presenting ability of all the APCs, suggesting that increased expression of class II MHC protein by IL-2 played an important role in HSAB presentation and T cell activation. Finally, early T cell receptor-dependent signals induced by HSAB or its analogs were examined by phosphotyrosine immunoblot analysis, and showed that tyrosine phosphorylation level of a 18-20 kD protein increased upon stimulation.

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Efficient Generation of BLCL Expressing Foreign Antigen as Antigen-presenting Cells with Recombinant Retroviruses

  • Hyun-Il Cho;Soon-Young Pail;Il-Hoan OH;Kyun-Jung Ahn;Dong-Wook Kim
    • Journal of Microbiology
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    • v.39 no.4
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    • pp.300-304
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    • 2001
  • Epstein-Barr Virus(EBV)-transformed lymphoblastoid B cell lines, BLCL which expresse antigens, are potential antigen-presenting cells(APCs) for the induction of CTL in vitro. However transfection of BLCLs with subsequent selection by antibiotics is notoriously difficult because plating efficiencies of BLCLsare reported to be 1% or less. To generated stable transfectants of BLCLs we produced high titers of retroviruess encoding pp 65 antigen of human cytomegalovirus of foreign antigens and trans-duced them of BLCLs. The pp 65 gene was cloned into the retroviral vector pLXSN. The recombinant retroviral vector was transfected to ecotropic packaging cell line, CP&E86, and this polyclonal recom-binant retrovirus was transduced to PA317 that is amphotropic pakaging cell line. The titers of colned PA317 amphotropic retroviruses ranged from 5 to $\times$10$^{6}$ colony forming units (CFU)per ml (CFU/ml) We performed three rounds of consecutive transductions to BLCLs in order to improve the clon-ing effieiencies. The expression of recombinant HCMV-pp65 antigen was more than 20% after the final transduction. THe third-transduced BLCLs were easily selected in optimal concentration of G418. BLCLs expressing foreign antigens could be used as target cells for CTL assay and/or as APCs for induction of in vitro CTL responses specific for viral and tumor antigens.

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Effect of Lipofectin on Antigen-presenting Function and Anti-tumor Activity of Dendritic Cells (수지상세포의 항원제시 능력 및 항암활성에 미치는 Lipofectin의 영향)

  • Noh, Young-Woock;Lim, Jong-Seok
    • IMMUNE NETWORK
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    • v.6 no.2
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    • pp.102-110
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    • 2006
  • Background: Dendritic cells (DC) are professional antigen-presenting cells in the immune system and can induce T cell response against virus infections, microbial pathogens, and tumors. Therefore, immunization using DC loaded with tumor-associated antigens (TAAs) is a powerful method of inducing anti-tumor immunity. For induction of effective anti-tumor immunity, antigens should be efficiently introduced into DC and presented on MHC class I molecules at high levels to activate antigen-specific $CD8^+$ T cells. We have been exploring methods for loading exogenous antigens into APC with high efficiency of Ag presentation. In this study, we tested the effect of the cationic liposome (Lipofectin) for transferring and loading exogenous model antigen (OVA protein) into BM-DC. Methods: Bone marrow-derived DC (EM-DC) were incubated with OVA-Lipofectin complexes and then co-cultured with B3Z cells. B3Z activation, which is expressed as the amount of ${\beta}$-galactosidase induced by TCR stimulation, was determined by an enzymatic assay using ${\beta}$-gal assay system. C57BL/6 mice were immunized with OVA-pulsed DC to monitor the in vivo vaccination effect. After vaccination, mice were inoculated with EG7-OVA tumor cells. Results: BM-DC pulsed with OVA-Lipofectin complexes showed more efficient presentation of OVA-peptide on MHC class I molecules than soluble OVA-pulsed DC. OVA-Lipofectin complexes-pulsed DC pretreated with an inhibitor of MHC class I-mediated antigen presentation, brefeldin A, showed reduced ability in presenting OVA peptide on their surface MHC class I molecules. Finally, immunization of OVA-Lipofectin complexes-pulsed DC protected mice against subsequent tumor challenge. Conclusion: Our data provide evidence that antigen-loading into DC using Lipofectin can promote MHC class I- restricted antigen presentation. Therefore, antigen-loading into DC using Lipofectin can be one of several useful tools for achieving efficient induction of antigen-specific immunity in DC-based immunotherapy.

HLA-restricted and Antigen-specific CD8+ T Cell Responses by K562 Cells Expressing HLA-A*0201

  • Yun, Sun-Ok;Sohn, Hyun-Jung;Yoon, Sung-Hee;Choi, Hee-Baeg;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.6 no.4
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    • pp.179-184
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    • 2006
  • Background: Identification of antigen-specific T cells has yielded valuable information on pathologic process and the disease state. Assays for quantification of inflammatory cytokines or lytic-granule molecules have been generally used to evaluate antigen specific T cell response, however their applicability have been hampered due to the limited source of autologous antigen-presenting target cells (APC). Methods: K562, a leukemic cell line deficient of human leukocyte antigen (HLA), was transfected with a gene encoding HLA-A*02 (K562/ A*02) and its function as stimulator cells in inducing activation of HLA-matched T cells was evaluated by IFN-${\gamma}$ enzyme linked immunospot (ELISPOT) assay. Results: The stable transfectant K562/ A*02 pulsed with HLA- A*02 restricted peptide could specifically induce IFN-${\gamma}$ secretion by CD8+ T cells compared to no detectable secretion by CD4+ T cells. However, CD56+ NK cells secreted IFN-${\gamma}$ in both K562/ A*02 with peptide and without peptide. The number of IFN-${\gamma}$ secreted CD8+ T cells was increased according to the ratio of T cells to K562 and peptide concentration. Formalin-fixed K562/ A*02 showed similar antigen presenting function to live K562/ A*02. Moreover, K562/ A*02 could present antigenicpeptide to not only A*0201 restricted CD8+ T cells but also CD8+ T cells from A*0206 donor. Conclusion: These results suggest that K562/ A*02 could be generally used as target having specificity and negligible background for measuring CD8+ T cell responses and selective use of K562 with responsder matched HLA molecules on its surface as APC may circumvent the limitation of providing HLA-matched autologous target cells.

Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs

  • Shin, Seulmee;Hyun, Bobae;Lee, Aeri;Kong, Hyunseok;Han, Shinha;Lee, Chong-Kil;Ha, Nam-Joo;Kim, Kyungjae
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.35-41
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    • 2013
  • Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.