• 대한수의학회지
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• 제43권4호
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• pp.607-613
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• 2003

Dendritic cells (DCs) play an essential role in a variety of immune reactions involving $CD4^+$ T cells and have been used to enhance tumor-specific immune responses. Immunosuppression in patients with cancer includes the downregulation of function and number of DCs. Although DCs have been studied, the apoptosis of Des induced by anticancer drugs for chemotherapy remains largely uncharacterized. This study demonstrated that GM-CSF protects DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. After 6 - 10 days culture, DCs were characterized by specific surface marker, CD11c and MHC class II. MTT assay revealed that GM-CSF significantly enhanced the viability of DCs treated with 5-FU or mitomycin C. The percentage of dead cells of DCs was determined by cell size using FACScan and GM-CSF was clearly effective. However, GM-CSF did not increase the expression of MHC class II on viable DCs gated, suggesting that GM-CSF may differentially regulate critical factors involved in the function of DCs. For the quantitative analysis of apoptosis, annexin V-FITC staining was performed. 5-FU induced the apoptosis of DCs and GM-CSF significantly protects DCs from 5-FU-induced apoptosis. Taken together, the results in this study that GM-CSF has an anti-apoptosis effect on DCs may provide patients with cancer with clinical benefits to overcome the immunosuppression induced by the decrease of number and functional insufficiency of DCs.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.215-216
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• 2001

Mouse monoclonal antibody(mAb) with an antigen specificity for major histocompatibility complex class Il(MHC class II) was produced and secreted from tobacco cell suspension culture by successive sexual crossesu. Expression and secretion of assembled antibody was observed in transgenic tobacco cell suspension culture by wetern blot analysis.

• BMB Reports
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• 제56권3호
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• pp.140-144
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• 2023

While CD8⁺ cytotoxic T cells have long been considered the primary effector in controlling tumors, the involvement of CD4⁺ "helper" T cells in anti-tumor immunity has been underappreciated. The investigations of intra-tumoral T cells, fueled by the recent advances in genomic technologies, have led to a rethinking of the indirect role of CD4⁺ T cells that have traditionally been described as a "helper". Accumulating evidence from preclinical and clinical studies indicates that CD4⁺ T cells can acquire intrinsic cytotoxic properties and directly kill various types of tumor cells in a major histocompatibility complex class II (MHC-II)-dependent manner, as opposed to the indirect "helper" function, thus underscoring a potentially critical contribution of CD4⁺ cytotoxic T cells to immune responses against a wide range of tumor types. Here, we discuss the biological properties of anti-tumor CD4⁺ T cells with cytotoxic capability and highlight the emerging observations suggesting their more significant role in anti-tumor immunity than previously appreciated.

• 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.

• BMB Reports
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• 제47권5호
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• pp.241-248
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• 2014

CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to ${\alpha}{\beta}$ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of ${\alpha}{\beta}$ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant $V{\alpha}14-J{\alpha}18$ TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4167-4175
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• 2013

A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, Epi,Jen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.

• BMB Reports
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• 제45권9호
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• pp.538-543
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• 2012

We evaluated the expression of the costimulatory molecules CD80 and CD83 and major histocompatibility (MHC) class II induced by 2,4-dinitrofluorobenzene (DNFB) in the RAW 264.7 macrophage cell line. In contrast to the previously reported effect of DNFB on dendritic cells, CD86 expression did not change. Furthermore, we observed that the CD83 expression level transiently increased and then decreased. Induction of CD80 and MHC class II molecule expression and a decrease in CD83 expression by DNFB in vitro were also confirmed in splenocytes of BALB/c and NC/Nga mice. However, DNFB did not influence CD83 expression in peritoneal $CD11b^+$ cells from BALB/c or NC/Nga mice. Detailed in vivo experiments and further studies on the possible contribution of $CD11b^+$ cells to induce atopic dermatitis (AD) would be helpful to attain a better understanding of AD pathogenesis.

• 생명과학회지
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• 제28권6호
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• pp.753-763
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• 2018

Cathepsin은 리소좀에 존재하는 효소로, 엔도좀-리소좀 경로를 통하여 손상된 단백질의 분해를 유도한다. 이러한 cathepsin은 활성화되는 촉매 잔기 위치(catalytic residue site)에 따라 cysteine, aspartate, serine cathepsin으로 나뉜다. 다양한 암세포에서 cysteine cathepsin은 유전자 증폭이나 전사, 번역, 전사 후 단계를 통해 높은 발현을 유지한다. 특히 cathepsin S의 경우, 다른 cysteine cathepsin과 달리 중성 pH 환경에서도 안정적으로 활성도를 유지하며 특정 조직에서 발현이 제한적이라는 특징을 가지고 있기 때문에 질병의 미세환경에서 중요한 역할을 한다. 면역세포에서의 cathepsin S는 불변 사슬(invariant chain)을 분해하여 항원 제시에 중요한 MHC class II의 활성화를 통해 면역 반응을 조절하며, 암세포에서의 cathepsin S는 전이와 혈관신생을 조절함으로써 암세포의 성장을 증가시키는 역할을 한다. Cathepsin S의 발현 조절에 문제가 생기면 암, 관절염, 심혈관 질환을 포함한 많은 병리학적 현상에 영향을 미친다. 특히 암세포에서 cathepsin S의 발현 억제와 결함은 혈관신생을 억제시킬 뿐만아니라, 암세포의 성장과 전이를 감소시키고 세포사멸을 유도한다. 따라서, cathepsin S는 암 치료에 있어 좋은 표적이 될 수 있다.

• 한국식품과학회지
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• 제50권5호
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• pp.511-516
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• 2018

본 연구는 꾸지뽕 열매로부터 분리한 조다당류(CTPS)가 초기 면역반응에 중추적인 역할을 수행하는 큰포식세포에서 활성화를 유도하는지에 관한 여부를 알아보기 위하여 선천 및 적응면역에서 중추적인 역할을 수행하는 큰포식세포에 CTPS를 처리하여 세포 증식률, 산화질소 분비능 및 사이토카인($TNF-{\alpha}$ 및 IL-6) 분비능이 증가되는 것을 확인하였다. 또한 활성화된 큰포식세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식세포의 항원 제시에 밀접한 관련이 있는 주조직적합성 복합체(MHC class I 및 II)의 발현이 CTPS 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 이러한 산화질소 분비능과 사이토카인의 증가 원인에 관한 면역기전 분석 결과, MAPKs의 인산화와 $NF-{\kappa}B$의 핵 내 이동성을 증가시켜 면역활성을 증가시키는 것으로 관찰되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.169-173
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• 2009

Ginsan, a Panax ginseng polysaccharide that contains glucopyranoside and fructofuranoside, has immunomodulatory effects. Although several biologic studies of ginsan have been performed, its effects on dendritic cells (DCs), which are antigen-presenting cells of the immune system, have not been studied. We investigated the immunomodulatory effects of ginsan on DCs. Ginsan had little effect on DC viability, even when used at high concentrations. Ginsan markedly increased the levels of production by DCs of IL-12 and TNF-${\alpha}$, as measured by ELISA. To examine the maturation-inducing activity of ginsan, we measured the surface expression levels of the maturation markers MHC class II and CD86 (B7.2) on DCs. It is interesting that ginsan profoundly enhanced the expression of CD86 on DC surfaces, whereas it increased that of MHC class II only marginally. In $^3H$-thymidine incorporation assays, ginsan-treated DCs stimulated significantly higher proliferation of allogeneic $CD4^+$ T lymphocytes than did medium-treated DCs. Taken together, our data demonstrate that ginsan stimulates DCs by inducing maturation. Because DCs are critical antigen-presenting cells in immune responses, this study provides valuable information on the activities of ginsan.