慢性乙型肝炎患者HBV核心区与聚合酶区特异性CTL表位变异分析

目的比较急性乙型肝炎、慢性乙型肝炎与慢性重型乙型肝炎患者HBV C蛋白和Pol蛋白特异性CTL表位变异的差异,以探讨乙型肝炎重症化和慢性化的可能机理。方法对516例乙型肝炎患者的血清进行HLA-A2和A11分型;用巢式PCR扩增血清HBV C基因与Pol基因并对PCR产物进行序列测定;根据HBV S基因序列,用VirusBlast软件鉴定患者感染的HBV基因型;用Vector NTI软件对目前已知的HLA-A2限制性的4个C蛋白和5个Pol蛋白特异性CTL表位与HLA-A11限制性的1个C蛋白表位进行序列分析。结果 247例（47.86%）患者HLA-A2阳性,其中AHB 67例,CHB 109例,CSHB 71例;220例（42.64%）患者HLA-A11阳性,其中AHB 67例,CHB 107例,CSHB 46例;CTL表位变异分析结果如下：①在3组HLA-A2阳性患者,表位变异发生率无显著性差异（P〉0.05）;②在三组HLA-A2阳性HBV B基因型患者,P455-463和P816-824表位变异有极显著性差异（P〈0.01）;③在三组HLA-A2阳性HBV C基因型患者,各表位变异无显著性差异;④在三组HLA-A11阳性患者,C88-96表位变异发生率有显著性差异（P〈0.05）,三组HBV C基因型患者,表位变异发生率有极显著性差异（P〈0.01）,而在HBV B基因型患者,各表位变异无显著性差异（P〉0.05）。结论某些HBV C蛋白和Pol蛋白特异性CTL表位在AHB、CHB和CSHB患者间变异有明显差异,并且受感染病毒基因型的影响。CTL表位变异可能与乙型肝炎的重症化和慢性化机制相关。

Mutation analysis of cytotoxic T lymphocyte epitopes derived from HBV core protein and polymerase protein in patients with hepatitis B

Objective To compare mutation occurrence of hepatitis B virus(HBV)core(C)protein and polymerase(Pol)protein specific cytotoxic T lymphocytes(CTL)epitopes among patients with acute(AHB),chronic(CHB)and chronic severe hepatitis B(CSHB).Methods HLA-A2 and HLA-A11 typing were performed in 516 patients with hepatitis B.Nested PCR was used to amplify HBV C gene and Pol gene followed by sequencing of PCR products.HBV genotyping was determined based on the S gene sequences.The mutations of 9 HLA-A2-restricted C pro...