Objective： With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 （IGFBP7） is very important for some research about tu...Objective： With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 （IGFBP7） is very important for some research about tumor metastasis. Because HLA-A2.1-expressing individuals cover 〉50% in the population of China, we aimed at identifying IGFBPT-encoded peptide presented by HLA-A2.1. Methods： In our study, a HLA-A2.1 restricted CTL epitope was identified by using the following two-step procedure： （a） computer-based epitope prediction from the amino acid sequence of IGFBP7 antigen; （b） Validation with epitope molecular modeling. Results： We obtained four epitopes with high immunogenicity scores by all of the three algorithms, i.e., BIMAS, SYFPEITH1 and IMTECH. Each of the four candidates satisfied the criteria of the HLA-A2.1- restricted CTL epitopes in molecular modeling analysis. Conclusion： The combination of BIMAS, SYFPEITHI and IMTECH method can improve the prediction efficiency and accuracy. Due to this research herein, this four epitopes have potential value for further studied, also have potential application in peptide-mediated immunotherapy. These epitopes may be useful in the design of therapeutic peptide vaccine for lung carcinoma and as immunotherapeutic strategies against lung carcinoma after identified by immunology experiment.展开更多
目的预测并筛选免疫反应性较强的四跨膜蛋白超家族成员1(transmembrane 4 L6 family member 1,TM4SF1)人类白细胞抗原A2(human leukocyte antigen A2,HLA-A2)限制性T淋巴细胞(cytotoxic lymphocyte,CTL)表位肽。方法联合4种软件(BIMAS、...目的预测并筛选免疫反应性较强的四跨膜蛋白超家族成员1(transmembrane 4 L6 family member 1,TM4SF1)人类白细胞抗原A2(human leukocyte antigen A2,HLA-A2)限制性T淋巴细胞(cytotoxic lymphocyte,CTL)表位肽。方法联合4种软件(BIMAS、SYFPEITHI、IEDB、PROPRED I)对TM4SF1的HLA-A2限制性CTL表位进行预测,并采用预培养法酶联免疫斑点法(enzyme-linked immunospot assy,ELISOPT)、直接法ELISOPT对所测得表位肽的免疫反应性进行鉴定。结果 4种不同软件共预测出10条表位多肽,对其中4条(P1、P2、P8、P10)进行免疫反应性验证。多肽活化CTL能力结果显示,预培养法ELISPOT产生斑点形成细胞(spvt forming cell,SFC)的净值T明显高于直接法ELISPOT:[(阳性对照肽:322±8 vs 169±22,P<0.05)、(多肽P1:114±10 vs 39±7,P<0.05)、(多肽P10:156±31 vs 52±8,P<0.05)]。单个活化CTL细胞分泌INF-γ因子的水平检测结果显示,预培养法ELISPOT产生斑点的平均大小明显大于直接法ELISPOT[(阳性对照肽:21.91±2.45 vs 13.80±1.76,P<0.05)、(多肽P1:12.90±0.88 vs 8.31±1.40,P<0.05)、(多肽P10:17.50±3.85 vs 11.96±0.61,P<0.05)]。表位多肽P1、P10均具有免疫原性,P10的免疫活性更高。结论预培养法ELISPOT检测多肽的免疫反应性较直接法ELISPOT灵敏性更高,多种软件联合ELISPOT预培养法可有效筛选出免疫反应性更强的卵巢癌相关抗原TM4SF1 HLA-A2限制性CTL优势表位,其中P10的免疫活性最高。展开更多
基金Supported by the Special fund of the National High Technology Research and Development Program of China (863 Program,2007AA02Z129)the National Natural Science Foundation of China (30672076 and 30800506)
文摘Objective： With the development of peptide-based cancer specific immunotherapy, the prediction of CTL epitopes from insulin-like growth factor-binding protein 7 （IGFBP7） is very important for some research about tumor metastasis. Because HLA-A2.1-expressing individuals cover 〉50% in the population of China, we aimed at identifying IGFBPT-encoded peptide presented by HLA-A2.1. Methods： In our study, a HLA-A2.1 restricted CTL epitope was identified by using the following two-step procedure： （a） computer-based epitope prediction from the amino acid sequence of IGFBP7 antigen; （b） Validation with epitope molecular modeling. Results： We obtained four epitopes with high immunogenicity scores by all of the three algorithms, i.e., BIMAS, SYFPEITH1 and IMTECH. Each of the four candidates satisfied the criteria of the HLA-A2.1- restricted CTL epitopes in molecular modeling analysis. Conclusion： The combination of BIMAS, SYFPEITHI and IMTECH method can improve the prediction efficiency and accuracy. Due to this research herein, this four epitopes have potential value for further studied, also have potential application in peptide-mediated immunotherapy. These epitopes may be useful in the design of therapeutic peptide vaccine for lung carcinoma and as immunotherapeutic strategies against lung carcinoma after identified by immunology experiment.
文摘目的预测并筛选免疫反应性较强的四跨膜蛋白超家族成员1(transmembrane 4 L6 family member 1,TM4SF1)人类白细胞抗原A2(human leukocyte antigen A2,HLA-A2)限制性T淋巴细胞(cytotoxic lymphocyte,CTL)表位肽。方法联合4种软件(BIMAS、SYFPEITHI、IEDB、PROPRED I)对TM4SF1的HLA-A2限制性CTL表位进行预测,并采用预培养法酶联免疫斑点法(enzyme-linked immunospot assy,ELISOPT)、直接法ELISOPT对所测得表位肽的免疫反应性进行鉴定。结果 4种不同软件共预测出10条表位多肽,对其中4条(P1、P2、P8、P10)进行免疫反应性验证。多肽活化CTL能力结果显示,预培养法ELISPOT产生斑点形成细胞(spvt forming cell,SFC)的净值T明显高于直接法ELISPOT:[(阳性对照肽:322±8 vs 169±22,P<0.05)、(多肽P1:114±10 vs 39±7,P<0.05)、(多肽P10:156±31 vs 52±8,P<0.05)]。单个活化CTL细胞分泌INF-γ因子的水平检测结果显示,预培养法ELISPOT产生斑点的平均大小明显大于直接法ELISPOT[(阳性对照肽:21.91±2.45 vs 13.80±1.76,P<0.05)、(多肽P1:12.90±0.88 vs 8.31±1.40,P<0.05)、(多肽P10:17.50±3.85 vs 11.96±0.61,P<0.05)]。表位多肽P1、P10均具有免疫原性,P10的免疫活性更高。结论预培养法ELISPOT检测多肽的免疫反应性较直接法ELISPOT灵敏性更高,多种软件联合ELISPOT预培养法可有效筛选出免疫反应性更强的卵巢癌相关抗原TM4SF1 HLA-A2限制性CTL优势表位,其中P10的免疫活性最高。
