• 제목/요약/키워드: MHC class-I

검색결과 111건 처리시간 0.026초

Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells

  • Kim, Hyun-Jin;Lee, Young-Hee;Im, Sun-A;Kim, Kyungjae;Lee, Chong-Kil
    • IMMUNE NETWORK
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    • 제10권3호
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    • pp.92-98
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    • 2010
  • Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

보중익기탕의 T세포 증식 유도 효과 (Effect of Bu-Zhong-Yi-Qi-Tang on Proliferation of T Cells)

  • 채수연;신성해;하미혜;조성기;김성호;변명우;이성태
    • 한국식품영양과학회지
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    • 제33권7호
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    • pp.1085-1091
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    • 2004
  • 먼저 OVA항원에 대해 특이적으로 증식반응을 나타내는 T세포주를 수립하였고, 수림된 세포주는 세포 표면 단백질이 CD4$^{+}$CD8$^{-}$이며 IL-2와 IFN-${\gamma}$를 분비하는 Type I에 속하는 보조 T세포(Thl)인 것을 확인하였다. 보중익기탕의 total 분획은 OVA항원에 대해 특이적으로 반응하는 Thl세포의 증식반응을 증가시키는 효과를 나타내지 않았으며 고농도에서 오히려 증식반응을 억제하였다. 그러나, 보중익기탕의 polysaccharide 분획은 전반적 인 농도에서 T세포의 증식반응을 유의하게 증가시키는 효과가 있는 것으로 나타났다. 보중익기탕의 polysaccharide 분획을 첨가하였을 때 T세포의 IL-2 분비량은 대조군보다 약간 적었지만, IFN-${\gamma}$ 분비량은 대조군보다 증가하였다. 그리고, 분비된 IL-2와 결합하는 T세포의 IL-3 수용체 발현양도 증가하는 것으로 나타났다. 또한, 항원제시세포의 MHC class II의 발현양도 증가시켰다. 이상의 결과로 보중익기탕의 polysaccharide분획은 T세포의 IL-2수용체 발현양을 증가시키고, 항원제시세포의 MHC classs II의 발현양을 증가시켜서 T세포의 증식반응을 증가시키는것으로 생각된다 그리고 보중익기탕이 생체 면역반응에 미치는 보다 정확한 효과를 평가하기 위해서는 직접 살아있는 실험동물에 투여하는 in vivo 실험이 필요하다.

측두엽 간질환자의 혈청에서 프로테오믹스기법을 활용한 질병관련 단백질 동정 (Proteomic analysis of human serum from patients with temporal lobe epilepsy)

  • 이창우;유승택;최하영;고은정;곽용근
    • Clinical and Experimental Pediatrics
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    • 제52권5호
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    • pp.567-575
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    • 2009
  • 목적 : 간질은 전세계인구의 0.5%에서 발병하며 유전적 성향이 많고, 이는 중추신경계의 과 흥분성에 기인한다고 알려져 있다. 최근 프로테오믹스기법의 발달로 질병관련 단백질 동정이 활발히 연구되어지고 있다. 더불어, 간질의 진단은 영상기법 및 뇌파 분석 등이 이용되고 있으나, 가장 손쉽고 경제적인 혈청단백질을 이용한 진단법은 확립되어 있지 못하다. 그러므로 본 연구에서는 측두엽 간질환자의 혈장 단백질을 분석하여 간질의 진단 표지단백질 및 질병관련단백질을 발굴하고자 하였다. 방 법 : 저자들은 8명의 측두엽 간질환자와 8명의 정상인 혈청을 비교하였다. 결 과 : 간질환자의 혈청에서 정상 혈청단백질과 유의하고 일관성 있는 차이를 보이는 12개의 단백질을 발견하였다. 그 중, 6개의 단백질을 동정하였고, 6개의 단백질은 동정하지 못하였다. 더불어, haptoglobin Hp2, PRO2675, immunoglobulin heavy chain constant region gamma 2와 1개의 명명되지 않은 단백질 및 3개의 미지의 단백질을 포함한 7개의 단백질은 간질환자의 혈액에서 증가하였다. 반면, MHC class I antigen, plasma retinol-binding protein precursor 및 3개의 미지의 단백질을 포함한 5개의 단백질은 감소하였다. 결 론 : MHC class I antigen, immunoglobulin heavy chain constant region gamma 2 및 수술 전에 증가하였던 3개의 미지의 단백질 중에서 1개, 감소하였던 3개의 미지의 단백질 중에서 2개를 포함한 모두 5개의 단백질은 간질을 일으키는 뇌 부위 절제 후 정상으로 회복되었다. 이는 이런 단백질들을 측두엽 간질의 진단 및 경과관찰인자로서, 활용할 수 있음을 시사한다. 나아가, 이러한 단백질들은 간질의 병태 생리 연구 및 새로운 치료약물개발의 표적 단백질로 활용될 수 있을 것이다.

C형 간염 바이러스 감염 간암 세포주와 T 림프구의 상호작용에 대한 연구 (The Interaction between HCV-Infected huh7.5 Cells and HCV-Specific T Cells)

  • 강효정;조효선
    • 미생물학회지
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    • 제50권2호
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    • pp.169-172
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    • 2014
  • 최근 인간 간암세포주(human hepatoma cells)를 이용하여 C형 간염 바이러스(hepatitis C virus, HCV)의 복제가 가능한 세포배양모델(cell culture system)이 확립되었다. 본 연구에서는 인간 간암세포주 중 huh7.5 cell (human hepatoma 7.5 cells)과 C형 간염 바이러스인 J6/JFH1 clone (2a 유전자형)를 이용하여 감염 가능한 세포배양모델을 확립하였다. 또한, HCV 감염 간암세포주의 HCV 특이 T 림프구에 대한 항원제시(antigen presentation) 가능성을 살펴보았다. 외부에서 전달된 HCV 항원일 경우 간암세포주의 HCV 특이 T 림프구에 대한 항원제시로 T 림프구의 활성이 가능하였으나, HCV 감염 간암세포주의 경우 T 림프구의 활성을 억제하였다. 이러한 HCV 특이 T 림프구의 활성억제와 HCV 감염 간암세포주 항원제시능의 상관성을 알아보기 위해 HCV 감염 간암세포주의 주조직적합성복합체(major histocompatibility complex, MHC) 발현변화를 측정하였으나 HCV 감염은 간암세포주의 MHC 발현변화에 영향을 미치지 않았다.

한국 재래 닭 품종 특성 및 초기성장 개량을 위한 분자표지 개발 (Characteristics and Improving Breed of Economic Traits of Korea Native Chicken)

  • 오재돈;박미현;공홍식;이학교;전광주;연성흠;상병돈;최철환;조병욱
    • 한국가금학회지
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    • 제32권1호
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    • pp.29-34
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    • 2005
  • 본 연구는 한국 재래 닭의 유전적 특성을 분자표지를 이용하여 그 차이를 규명하고 초기성장에 미치는 영향을 분석하여 이를 이용한 재래닭의 개량을 목적으로 실시하였다. MHC class II B-LB 유전자 내의 염기변이체가 경제형질에 미치는 영향에 대하여 연구하였다. MHC class II B-LB유전자 내 400 bp 크기의 유전자를 증폭하여 염기서열 분석과 제한효소 처리를 이용한 다형성 분석을 실시하였다. 연구결과 두 개의 제한효소 절단지역이 발견되었으며 427 지역을 Type I 으로 651 지역은 Type II로 정하여 RFLP 분석을 실시하였다. Type I지역의 유전자형은 TT, TC, CC로 나타났으며, TypeII 지역의 유전자형은 MM, Mm, mm으로 나타났다. TC와 Mm 유전자형이 다른 유전자형과 비교하였을 때 한국재래 닭에서 높은 출현빈도를 보였다(0.8, 0.88). 유전자형이 한국 재래 닭의 150일령 체중에 미치는 영향을 분석한 결과 CC와 Mm 유전자형에서 통계적 유의성이 도출되었다 (P<0.05). 따라서 본 연구의 결과를 이용하여 한국 재래 닭의 유전적 특성을 규명할 수 있으며 초기 성장이 높은 성적을 나타내는 CC, Mm 유전자형을 개량에 이용하게 된다면 큰 효과를 얻을 수 있을 것으로 사료되어진다. 본 연구의 결과는 차후 한국 재래 닭의 과학적이고 지속적인 유전자원의 보존과 육종 전략에 있어 매우 유용하게 활용될 것으로 기대된다.

Use of Cell-Penetrating Peptides in Dendritic Cell-Based Vaccination

  • Sangho Lim;Ja-Hyun Koo;Je-Min Choi
    • IMMUNE NETWORK
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    • 제16권1호
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    • pp.33-43
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    • 2016
  • Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4+ and CD8+ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

Analysis of Swine Leukocyte Antigen Haplotypes in Yucatan Miniature Pigs Used as Biomedical Model Animal

  • Choi, Nu-Ri;Seo, Dong-Won;Choi, Ki-Myung;Ko, Na-Young;Kim, Ji-Ho;Kim, Hyun-Il;Jung, Woo-Young;Lee, Jun-Heon
    • 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.

Clinico-Pathological Significance of MHC-I Type Chain-associated Protein A Expression in Oral Squamous Cell Carcinoma

  • Wang, Jie;Li, Chao;Yang, Dan;Jian, Xin-Chun;Jiang, Can-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권2호
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    • pp.715-718
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    • 2012
  • The current research concerns the clinicopathological significance of MHC class I chain-related protein A (MICA) expression in oral squamous cell carcinomas (OSCCs). The expression and location of MICA protein in 14 normal oral mucous and 45 cancerous and para-cancerous tissues were assessed by immunohistochemistry and levels of MICA mRNA expression in 29 cancerous and para-cancerous tissues were determined by the real-time polymerase chain reaction. Data were analyzed with the SPSS16.0 software package. MICA was found to be located in the cytoplasm and plasma membrane. Expression was higher in para-cancerous than in cancerous tissues (P < 0.05). However, no statistical difference was found between the following: 1) para-cancerous tissue with normal mucosa; 2) normal mucosa with cancerous tissue;and 3) among different clinicopathological parameters in OSCC (P > 0.05). The level of MICA mRNA was higher in OSCCs than in para-cancerous tissues, and was correlated with the regional lymph node status and disease stage (P < 0.05). The levels of MICA protein and mRNA expression differ among normal oral mucosa, para-cancerous tissue, and cancerous tissue. MICA may contribute to the tumorigenesis and progression of OSCC.

The Anti-tumor Activity of Vitamin C via the Increase of Fas (CD95) and MHC I expression on Human Stomach Cancer Cell Line, SNU1

  • Yu, Yeon-Sil;Bae, Se-Yeon;Kim, Hye-Min;Kim, Ye-Jin;Chu, Nag-Bum;Chu, Nag-Kyun;Kang, Jae-Seung;Lee, Wang-Jae
    • IMMUNE NETWORK
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    • 제11권4호
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    • pp.210-215
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    • 2011
  • It is already known that high concentration of vitamin C induces apoptosis on tumor cells. However, there is no report regarding the function of vitamin C on the modulation of immune susceptibility of cancer. Therefore, we investigated whether vitamin C can modulate immune susceptibility of tumor cells, especially on the induction of Fas-mediated apoptosis. First, the optimal concentration of vitamin C, which cannot induce damages on tumor cells for 36 hrs. We found that 2 mM of vitamin C did not show harmful effect. In addition, the optimal concentration of agonistic anti-Fas Abs for 18 hrs was examined. As a result, 400 ng/ml of agonistic anti-Fas Abs did not induce apoptosis on tumor cells. Next, we tried to find the effect of 2 mM of vitamin C on the modulation of the susceptibility to agonistic anti-Fas Abs. When tumor cells were cultured with 400 ng/ml of agonistic anti-Fas Abs for 18 hrs, after pre-treatment with 2 mM of vitamin C for 24 hrs, viability of cells was decreased. Interestingly, we found that the expression of Fas (CD95) and MHC class I was increased by the treatment of vitamin C. Taken together, vitamin C increases the susceptibility of tumor cells to anti-Fas Abs and the expression of Fas (CD95) and MHC class I on tumor cells.

Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

  • Sang-Hyun Kim;Ha-Eun Park;Seong-Un Jeong;Jun-Hyeok Moon;Young-Ran Lee;Jeong-Ki Kim;Hyunseok Kong;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • 제21권6호
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    • pp.44.1-44.15
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    • 2021
  • Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2Kb complex-specific CD8+ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8+ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.