肿瘤血管内皮抗原TEM8的HLA-2.1限制性低亲和性CTL表位预测及改造分析

Prediction and modification analysis of low-affinity HLA-2.1 restricted CTL epitopes derived from tumor endothelial marker 8

目的 初步筛选肿瘤血管内皮标志物8(tumorendothelialmarker 8,TEM 8)HLA A2 1限制性低亲和性CTL表位,并预测修饰后的表位与HLA A2 1之间亲和性的变化。方法 采用超基序、3D QSAR、蛋白酶解预测等相结合的办法筛选HLA A2 1限制性低亲和性CTL表位,并通过氨基酸置换适当修饰,最后对部分候选的多肽进行分子动力学模拟。结果 筛选出8个低亲和性CTL候选表位,经修饰后的表位与HLA A2 1之间的亲和性均有不同程度的提高。结论 初步预测和修饰的表位系列可为下一步实验提供了依据。

Objective To screen the possible HLA-A2.1 restricted low-affinity CTL epitopes derived from TEM8 and to predict the possible change of the affinity between epitope and the HLA-A2.1 molecule when the epitope is modified. Methods HLA-A2.1 restricted low-affinity CTL epitopes were predicted by CTL epitope-prediction-software based on supermotif, 3D-QSAR and proteasome cleavage probability. The candidates were modified by amino acid substitution and analyzed by computer. Six peptides were modeled by molecular dynamic simulation program. Results Eight low-affinity CTL candidate epitopes were selected out, and the affinity of the modified epitopes with HLA-A2.1 improved. Conclusion These data are very valuable for further experiments.