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1.
目的预测猪肌生成抑制素去信号肽蛋白的二级结构和B细胞优势抗原表位,为生产该蛋白的单克隆抗体、建立噬菌体抗体库、研制针对该基因的表位多肽疫苗、表位核酸疫苗等奠定基础。方法根据猪肌生成抑制素去信号肽蛋白氨基酸序列,应用7种参数和方法分析预测二级结构和抗原表位,包括Garnier-Robson、Chou-Fasman、Karplus-Schulz、Kyte-Doolittle、Emini、Jameson-Wolf及吴氏综合预测方法。结果MSTN去信号肽蛋白存在多个潜在的抗原表位位点,其中B细胞抗原优势表位可能在1-11、41-55、57-64、62-90、99-104、138-144、193-200、202-212、235-243区段或其附近,此结果将为进一步鉴定和合成多肽疫苗和表位核酸疫苗制备抗猪MSTN蛋白抗体提供依据,并为研究MSTN结构和功能奠定基础。  相似文献   

2.
目的预测白念珠菌细胞壁蛋白Csp37的抗原表位,分析其作为疫苗靶点的免疫原性。方法采用生物信息学方法对Csp37蛋白的抗原表位进行预测,利用ProtParam网络服务器分析蛋白基本理化性质,SignaIP 3.0预测信号肽,TMHMM软件预测跨膜区,GOR4在线分析蛋白二级结构,DNAStar预测分析亲水性、可塑性、表面可及性和氨基酸抗原指数,使用在线工具ABCPred预测B细胞抗原表位,Syfpeithi预测T细胞抗原表位。最后,综合分析B细胞和T细胞共有抗原表位。结果预测白念珠菌细胞壁蛋白Csp37的B细胞表位9个和T细胞表位8个,以及共有的优势抗原表位5个,共同优势区域为:45-48,76-78,153-158,222-225,303-305位氨基酸。结论白念珠菌细胞壁蛋白Csp37含有丰富的抗原表位,具有诱导细胞免疫应答和体液免疫应答的潜能,可以作为疫苗研究的新靶点。  相似文献   

3.
对2例HCV持续性感染者2个时间点NS3区C末端克隆测序,研究HCV NS3蛋白一个辅助T细胞表位(氨基酸位1248-1261)在HCV感染者体内的保守性;人工合成该表位进行淋巴细胞增殖试验和抑制试验,观察该表位引起免疫应答的水平和特点;通过"刺激-休息-刺激"多轮循环建立该表位特异性的T细胞系,并用流式细胞仪鉴定表型.结果发现该表位在2个病人2个时间点均未变化;观察的2例HCV持续性感染者和1例感染恢复者均对该表位有较强CD4+T细胞应答.建立了针对该表位的表型均一的CD4+辅助T细胞系.本研究提示该表位是一个序列保守的强辅助T细胞表位,对HCV T细胞疫苗的研制有一定意义.  相似文献   

4.
表达轮状病毒SA11株Vp4的抗原表位诱导病毒中和抗体生成   总被引:5,自引:0,他引:5  
以昆虫病毒Flockhousevirus(FHV)外壳蛋白为载体的外源抗原表位表达系统(FHV-RNA2载体系统).在重组杆状病毒和重组pET系统中构建和表达了SA11Vp4胰酶切割位点两侧和重叠切割位点3个抗原表位氨基酸序列(抗原表位A,aa223~242;抗原表位B,aa243~262;抗原表位C,aa234~251),并对其免疫原性进行了研究。结果表明:这3个抗原表位能诱导动物产生抗同源氨基酸序列的抗体和抗同源病毒(SA11)感染性的血清中和抗体。研究结果提示:RVVp4胰酶切割位点区氨基酸序列除了具有胰酶切割增强病毒感染力外,还具有诱导动物机体产生血清中和抗体的能力,是RV重组抗原表位亚单位疫苗研究中重要的抗原表位氨基酸序列。  相似文献   

5.
肿瘤干细胞具有肿瘤形成、自我更新和抗化疗的特性,因而受到广泛关注和研究。CD133作为重要的肿瘤干细胞标志物与肿瘤细胞的干性与恶性密切相关。本研究筛选并且鉴定了CD133的3个H2-Kd限制性的细胞毒性T细胞 (CTL) 的表位,分别是CD133419–428、CD133702–710和CD133760–769。将重组热休克蛋白gp96为佐剂联合CD133表位制备表位疫苗,将疫苗免疫CD133+白血病移植的小鼠后引发抗肿瘤的特异性T细胞免疫应答。转输CD133表位特异的T细胞同样可以抑制小鼠淋巴瘤的生长。该研究为设计抗CD133+的白血病和其他肿瘤的表位疫苗提供了依据。  相似文献   

6.
HCV分离株主要分为4个基因型(HCV Ⅰ~Ⅳ),各型间的氨基酸及核苷酸组成同源性均小于80%, 氨基酸变异率分别为C 8%,E1 35%,E2/NS1 53%,NS3 27%,NS4 35%,NS5 39%.不同型别的HCV有不同的地区分布特征.根据HCV表达产物多肽的保守性、亲水性、抗原性及空间构型等特性,已在HCV表达产物中鉴定出一些高度保守的候选B细胞表位及T细胞表位, 其中B细胞表位一般为12~40肽, T细胞表位一般为7~9肽, 这些B/T细胞保守表位的鉴定, 将有助于推动HCV的免疫治疗及疫苗研究的发展.  相似文献   

7.
为了研制口蹄疫抗原表位突变标记疫苗,本研究以含有Asia 1型口蹄疫病毒(FMDV)c DNA全长的感染性克隆p Asia 1-FMDV作为骨架,将3D蛋白中第27位氨基酸的H和31位的氨基酸N分别突变成Y和R,从而突变3D蛋白的一个抗原表位,将构建的带有突变表位的重组质粒转染BHK-21细胞,成功拯救出一株突变FMDV。经比较后发现,重组病毒的生物学特性与亲本毒株相似。病毒中和试验结果显示,抗重组病毒的血清与亲本病毒有良好的反应性。Western blotting结果表明重组病毒诱导的抗体能与突变的表位合成肽反应而不与野生型病毒的表位合成肽发生反应,从而区分重组病毒与亲本病毒。综上所述,这株抗原表位突变FMDV有望作为口蹄疫标记疫苗候株进一步评估。  相似文献   

8.
肿瘤干细胞具有肿瘤形成、自我更新和抗化疗的特性,因而受到广泛关注和研究。CD133作为重要的肿瘤干细胞标志物与肿瘤细胞的干性与恶性密切相关。本研究筛选并且鉴定了CD133的3个H2-K~d限制性的细胞毒性T细胞(CTL)的表位,分别是CD133_(419–428)、CD133_(702–710)和CD133_(760–769)。将重组热休克蛋白gp96为佐剂联合CD133表位制备表位疫苗,将疫苗免疫CD133~+白血病移植的小鼠后引发抗肿瘤的特异性T细胞免疫应答。转输CD133表位特异的T细胞同样可以抑制小鼠淋巴瘤的生长。该研究为设计抗CD133~+的白血病和其他肿瘤的表位疫苗提供了依据。  相似文献   

9.
疫苗是预防百日咳(pertussis)的最有效措施,但无细胞百日咳疫苗接种后免疫力的迅速衰退是近年来百日咳发病率上升的原因之一。百日咳毒素(pertussis toxin, PT)是由百日咳鲍特菌(Bordetella pertussis)分泌的主要毒力因子,具有多种生物学活性。在无细胞百日咳疫苗设计初期,为确保疫苗的有效性,抗PT的单克隆抗体(单抗)常被用来检测PT表面重要的抗原表位。研究表明,与天然PT特异性结合的部分单抗无法识别经化学方法脱毒后的PT,提示化学脱毒会改变疫苗中PT的一些抗原表位,进而影响疫苗保护效果。现结合单抗可用来研究抗体干扰PT功能的分子机制,对机体在感染百日咳后的保护性免疫机制进行综述,以期为无细胞百日咳疫苗的进一步改进及开发人源化抗PT单抗治疗百日咳提供科学依据。  相似文献   

10.
【背景】S蛋白是猪流行性腹泻病毒(Porcine Epidemic Diarrhea Virus,PEDV)的主要结构蛋白和免疫原性蛋白,在前期的研究中,本课题组在S蛋白的胞内区鉴定到2个包含线性B细胞表位的短肽。【目的】鉴定PEDV S蛋白胞内区线性B细胞表位的最小基序。【方法】原核表达2个短肽的每次后移1个氨基酸的系列8肽,以兔抗S蛋白血清为一抗,通过Western Blot筛选阳性反应8肽,鉴定S蛋白胞内区线性B细胞表位的最小基序。【结果】S蛋白胞内区的2个包含线性B细胞表位的短肽共享一个表位,该表位的最小基序为1371QPYE1374。同源性分析显示该B细胞表位基序为保守性表位。【结论】确定了S蛋白胞内区线性B细胞表位的最小基序为1371QPYE1374;S蛋白抗原表位的鉴定有助于提高对其结构和功能的理解。  相似文献   

11.
Low HDL-C levels are associated with atherosclerosis and non-alcoholic steatohepatitis, and increased levels may reduce the risk of these diseases. Inhibition of cholesteryl ester transfer protein (CETP) activity is considered a promising strategy for increasing HDL-C levels. Since CETP is a self-antigen with low immunogenicity, we developed a novel CETP vaccine (Fc-CETP6) to overcome the low immunogenicity of CETP and for long-term inhibition of CETP activity. The vaccine consists of a rabbit IgG Fc domain for antigen delivery to antigen-presenting cells fused to a linear array of 6 repeats of a CETP epitope to efficiently activate B cells. Rabbits were fed a high fat/cholesterol (HFC) diet to induce atherosclerosis and NASH, and immunized with Fc-CETP6 vaccine. The Fc-CETP6 vaccine successfully elicited anti-CETP antibodies and lowered plasma CETP activity. The levels of plasma HDL-C and ApoA-I were higher, and plasma ox-LDL lower, in the Fc-CETP6-immunized rabbits as compared to the unimmunized HFC diet-fed rabbits. Pathological analyses revealed less lipid accumulation and inflammation in the aorta and liver of the Fc-CETP6-immunized rabbits. These results show that the Fc-CETP6 vaccine efficiently elicited antibodies against CETP and reduced susceptibility to both atherosclerosis and steatohepatitis induced by the HFC diet. Our findings suggest that the Fc-CETP6 vaccine may improve atherosclerosis and NASH and has high potential for clinical use.  相似文献   

12.
The plasma cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. There are conflicting views regarding whether or not excessive CETP activity is one of the risk factors of atherosclerosis. To study how much effect CETP can have on the profiles of plasma lipoproteins in vivo, we produced four strains of transgenic mouse that expressed different levels of human CETP gene. We analyzed seven groups of mice that had different levels of CETP expression. The cholesterol level of HDL, chylomicron (CM) and VLDL, intermediate density lipoprotein (IDL) and LDL were proportionally changed in association with plasma CETP concentrations (2.9 +/- 0.6 to 37.4 +/- 1.7 microg/ml) in an allelic dose-dependent manner. We further characterized one of the transgenic strains, CETP-4, by optimizing the experimental condition for the mouse model of atherosclerosis, and found that it would be useful for the development of therapeutics against atherosclerosis.  相似文献   

13.
Cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl esters (CEs) from atheroprotective high‐density lipoproteins (HDLs) to atherogenic low‐density lipoproteins (LDLs) or very‐low‐density lipoproteins (VLDLs). Inhibition of CETP raises HDL cholesterol (good cholesterol) levels and reduces LDL cholesterol (bad cholesterol) levels, making it a promising drug target for the prevention and treatment of coronary heart disease. Although the crystal structure of CETP has been determined, the molecular mechanism mediating CEs transfer is still unknown, even the structural features of CETP in a physiological environment remain elusive. We performed molecular dynamics simulations to explore the structural features of CETP in an aqueous solution. Results show that the distal portion flexibility of N‐terminal β‐barrel domain is considerably greater in solution than in crystal; conversely, the flexibility of helix X is slightly less. During the simulations the distal end of C‐terminal β‐barrel domain expanded while the hydrophilic surface increasing more than the hydrophobic surface. In addition, a new surface pore was generated in this domain. This surface pore and all cavities in CETP are stable. These results suggest that the formation of a continuous tunnel within CETP by connecting cavities is permitted in solution. Proteins 2013. © 2012 Wiley Periodicals, Inc.  相似文献   

14.
Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B-containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 1.060 g/ml). CETP activities in heterozygous FH (79 +/- 4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54 +/- 6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p less than 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins.  相似文献   

15.
Cholesteryl ester transfer protein (CETP) plays an important role in plasma lipoprotein metabolism through its ability to transfer cholesteryl ester, triglyceride, and phospholipid between lipoproteins. CETP is a member of a gene family that also includes bactericidal/permeability-increasing protein (BPI). The crystal structure of BPI shows it to be composed of two domains that share a similar structural fold that includes an apolar ligand-binding pocket. As structurally important residues are conserved between BPI and CETP, it is thought that CETP and BPI may have a similar overall conformation. We have previously proposed a model of CETP structure based on the binding characteristics of anti-CETP monoclonal antibodies (mAbs). We now present a refined epitope map of CETP that has been adapted to a structural model of CETP that uses the atomic coordinates of BPI. Four epitopes composed of CETP residues 215-219, 219-223, 223-227, and 444-450, respectively, are predicted to be situated on the external surface of the central beta-sheet and a fifth epitope (residues 225-258) on an extended linker that connects the two domains of the molecule. Three other epitopes, residues 317-331, 360-366, and 393-410, would form part of the putative carboxy-terminal beta-barrel. The ability of the corresponding mAbs to compete for binding to CETP is consistent with the proximity of the respective epitopes in the model. These results thus provide experimental evidence that is consistent with CETP and BPI having similar surface topologies.  相似文献   

16.
Qi G  Li J  Wang S  Xin S  Du P  Zhang Q  Zhao X 《Peptides》2011,32(4):790-796
Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future.  相似文献   

17.
Reduced estrogen levels result in loss of protection from coronary heart disease in postmenopausal women. Enhanced and diminished atherosclerosis have been associated with plasma levels of cholesteryl ester transfer protein (CETP); however, little is known about the role of CETP-ovarian hormone interactions in atherogenesis. We assessed the severity of diet-induced atherosclerosis in ovariectomized (OV) CETP transgenic mice crossbred with LDL receptor knockout mice. Compared with OV CETP expressing ((+)), OV CETP non-expressing ((-)) mice had higher plasma levels of total, VLDL-, LDL-, and HDL-cholesterol, as well as higher antibodies titers against oxidized LDL. The mean aortic lesion area was 2-fold larger in OV CETP(-) than in OV CETP(+) mice (147 +/- 90 vs. 73 +/- 42 x 10(3) micro m(2), respectively). Estrogen therapy in OV mice blunted the CETP dependent differences in plasma lipoproteins, oxLDL antibodies, and atherosclerosis severity. Macrophages from OV CETP(+) mice took up less labeled cholesteryl ether (CEt) from acetyl-LDL than macrophages from OV CETP(-) mice. Estrogen replacement induced a further reduction in CEt uptake and an elevation in HDL mediated cholesterol efflux from pre-loaded OV CETP(+) as compared with OV CETP(-) macrophages. These findings support the proposed anti-atherogenic role of CETP in specific metabolic settings.  相似文献   

18.
Plasma cholesteryl ester transfer protein (CETP) has a profound effect on neutral lipid transfers between HDLs and apolipoprotein B (apoB)-containing lipoproteins when it is expressed in combination with human apoA-I in HuAI/CETP transgenic (Tg) rodents. In the present study, human apoA-I-mediated lipoprotein changes in HuAI/CETPTg rats are characterized by 3- to 5-fold increments in the apoB-containing lipoprotein-to-HDL cholesterol ratio, and in the cholesteryl ester-to-triglyceride ratio in apoB-containing lipoproteins. These changes occur despite no change in plasma CETP concentration in HuAI/CETPTg rats, as compared with CETPTg rats. A number of HDL apolipoproteins, including rat apoA-I and rat apoC-I are removed from the HDL surface as a result of human apoA-I overexpression. Rat apoC-I, which is known to constitute a potent inhibitor of CETP, accounts for approximately two-thirds of CETP inhibitory activity in HDL from wild-type rats, and the remainder is carried by other HDL-bound apolipoprotein inhibitors. It is concluded that human apoA-I overexpression modifies HDL particles in a way that suppresses their ability to inhibit CETP. An apoC-I decrease in HDL of HuAI/CETPTg rats contributes chiefly to the loss of the CETP-inhibitory potential that is normally associated with wild-type HDL.  相似文献   

19.
The human cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids among lipoproteins. In order to evaluate the effects of increased plasma CETP on lipoprotein levels, a human CETP minigene was placed under the control of the mouse metallothionein-I promoter and used to develop transgenic mice. Integration of the human CETP transgene into the mouse genome resulted in the production of active plasma CETP. Zinc induction of CETP transgene expression caused depression of serum cholesterol due to a significant reduction of high density lipoprotein cholesterol. There was no change in total cholesterol content in very low and low density lipoproteins. However, there was a decrease in the free cholesterol/cholesteryl ester ratio in plasma and in all lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of plasma cholesterol esterification. The results suggest that high levels of plasma CETP activity may be a cause of reduced high density lipoproteins in humans.  相似文献   

20.
Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and mediates HDL conversion. PLTP-overexpressing mice have increased atherosclerosis. However, mice do not express cholesteryl ester transfer protein (CETP), which is involved in the same metabolic pathways as PLTP. Therefore, we studied atherosclerosis in heterozygous LDL receptor-deficient (LDLR(+/-)) mice expressing both human CETP and human PLTP. We used two transgenic lines with moderately and highly elevated plasma PLTP activity. In LDLR(+/-)/huCETPtg mice, cholesterol is present in both LDL and HDL. Both are decreased in LDLR(+/-)/huCETPtg/huPLTPtg mice (>50%). An atherogenic diet resulted in high levels of VLDL+LDL cholesterol. PLTP expression caused a strong PLTP dose-dependent decrease in VLDL and LDL cholesterol (-26% and -69%) and a decrease in HDL cholesterol (-70%). Surprisingly, atherosclerosis was increased in the two transgenic lines with moderately and highly elevated plasma PLTP activity (1.9-fold and 4.4-fold, respectively), indicating that the adverse effect of the reduction in plasma HDL outweighs the beneficial effect of the reduction in apolipoprotein B (apoB)-containing lipoproteins. The activities of the antiatherogenic enzymes paraoxonase and platelet-activating factor acetyl hydrolase were both PLTP dose-dependently reduced ( approximately -33% and -65%, respectively). We conclude that expression of PLTP in this animal model results in increased atherosclerosis in spite of reduced apoB-containing lipoproteins, by reduction of HDL and of HDL-associated antioxidant enzyme activities.  相似文献   

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