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背景:GPIIb/IIIa是特发性血小板减少性紫癜患者最常见的血小板糖蛋白,已证实该蛋白独特型抗体结合血小板后会激活补体,破坏血小板。目的:以GPIIb/IIIa抗体为靶抗原,应用生物信息学软件对其CTL、Th细胞表位进行多参数预测。设计、时间及地点:开放性实验,于2008-03/08在珠江医院血液科实验室完成。材料:GPIIb/IIIa抗体的氨基酸序列由GENBANK公司提供。方法:分别应用SYFPEITHI,RANKPEP,BIMAS,SVMHC,PREDEP,MHCPRED,PROPRED软件对人和鼠源的血小板糖蛋白GPIIb/IIIa抗体蛋白进行HLA-A*0201,HLA-A*1101,HLA-A*2401限制性表位预测,经去除能引起自身免疫的已发表的多肽,取前者覆盖后二者的多肽为混合CTL表位,再联合软件predTAP、TAPPred的TAP结合预测结果,以及NetChop、MAPPP、PAProC软件的蛋白酶切位点预测结果,取能包含二者的多肽为CTL修正表位。用基于肽MHC-Ⅱ结合的算法Syfpeithi,RANKPEP,Mhcpred,HLAPRED进行HLA-DR的Th表位预测,最后取Th表位覆盖CTL修正表位,得到CTL、Th细胞混合表位。结果:从1740条多肽中筛选出5条人源抗人血小板糖蛋白GPIIb/IIIa抗体的CTL、Th细胞混合表位肽,即Anti-GPIIb/IIIa-Human的第1-15,24-38,50-64,65-81,109-121位;筛选出5条鼠源抗人血小板糖蛋白GPIIb/IIIa抗体的CTL、Th细胞混合表位肽,即Anti-GPIIb/IIIa-Mice的第1-15,26-40,46-60,68-82,93-107位。结论:根据血小板糖蛋白GPIIb/IIIa抗体预测的CTL、Th细胞优势抗原表位,可用于制备特异性抗体,可成为特发性血小板减少性紫癜新疫苗研究的靶点。
BACKGROUND: GPIIb / IIIa is the most common platelet glycoprotein in patients with idiopathic thrombocytopenic purpura. It has been demonstrated that this type of antibody binds to platelets and activates complement and destroys platelets. OBJECTIVE: To use multi-parameter prediction of CTL and Th cell epitopes with GPIIb / IIIa antibody as bio-informatics software. DESIGN, TIME AND SETTING: The open experiment was performed at Department of Hematology, Zhujiang Hospital from March to August 2008. Materials: The amino acid sequence of the GPIIb / IIIa antibody is provided by GENBANK. Methods: The platelet glycoprotein GPIIb / IIIa antibody of human and mouse were analyzed by HLA-A * 0201, HLA-A * 1101, HLA-A * 2401 The restricted epitope predicts that the peptides with the former covering the latter peptides are mixed CTL epitopes, combined with software predTAP, TAPPred TAP binding prediction results, and NetChop, MAPPP, PAProC The predicted result of protease cleavage site of the software, the peptide that can contain both is the CTL modified epitope. The HLA-DR Th epitopes were predicted by Sykpeithi, RANKPEP, Mhcpred and HLAPRED based on peptide MHC-Ⅱ binding. Finally, Th epitopes were used to cover the CTL modified epitopes to obtain CTL and Th cell mixed epitopes. RESULTS: CTL and Th cell mixed epitope peptides of 5 human anti-human platelet glycoprotein GPIIb / IIIa were screened from 1740 peptides, that is, 1-15,24-38 of Anti-GPIIb / IIIa-Human, 50-64, 65-81 and 109-121. The CTL and Th cell mixed epitope peptide of 5 murine anti-human platelet glycoprotein GPIIb / IIIa antibodies were screened, that is, 1-15 of Anti-GPIIb / IIIa-Mice, 26-40, 46-60, 68-82, 93-107. Conclusions: CTL and Th cell epitopes predicted by platelet glycoprotein GPIIb / IIIa antibody can be used to prepare specific antibodies, which may be the target of a new vaccine for idiopathic thrombocytopenic purpura.