HIV-1 pol抗原HLA-A*0201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-A0201 restricted CTL epitopes derived from HIV-1 pol antigen

目的:初步筛选HIV-1pol抗原的HLA-A*0201限制性低亲和性CTL表位,预测并初步鉴定修饰后的表位与HLA-A*0201之间亲和性的变化。方法:采用超基序、蛋白酶解、HLA结合力等预测相结合的办法筛选HLA-A*0201限制性低亲和性CTL表位,通过氨基酸置换适当修饰,并以T2细胞检测HLA-A*0201分子与肽的亲和力和稳定性来评价修饰后表位。结果:筛选出的低亲和性CTL候选表位,经修饰后与HLA-A*0201之间的亲和性均有不同程度的提高。其中,YVSLSFPQI(pol52-60Y1),YVSQIIEQL(pol673-681Y1),YIQKETWEA(pol548-556Y1)HLA-A*0201呈高亲和力结合,同时肽-HLA-A*0201复合物半数解离时间(Dissociation Complex50,DC50)均大于8h。结论:预测的pol抗原表位经过修饰可能会成为潜在的HLA-A*0201限制性表位。

AIM： To screen the possible HLA-A ＊ 0201 restricted low-affinity CTL epitopes derived from HIV-1 pol antigen and to predict and identify the possible change of the affinity between epitope and the HLA-A ＊ 0201 molecule when the epitope is modified. METHODS： HLA-A ＊ 0201 restricted low-affinity CTL epitopes were predicted by CTL epitope prediction software based on super motif, proteasome cleavage probability, HLA affinity and so on. The candidates were modified acid substitution and analyzed by computer. T2 cells were used to determine the peptide by amino binding affinity and HLA-A ＊ 0201-peptide complex stability. RESULTS： Among the three predicted peptides by softer ware, YVSLSFPQI （pol52-60Y1）, YVSQIIEQL pol （673-681Y1）, YIQKETWEA （ po1548-556Y1 ） could bind to HLA-A ＊ 0201 with high affinity, and the dissociation time of 50% HLA-A ＊ 0201 peptide complex was over to 8 h. CONCLUSION： Our results suggest that the three predicted peptides, as modification, might be HLA-A ＊ 0201 restricted CTL epitopes.