HLA-肽复合物研究HBV/C区变异对HLA-A2限制性表位的影响  

Influence of Hot spot mutations of HBV/C gene on CTL epitopes by HLA-A2-peptide complexes

作　　者：周最明[1] 郭亚兵[1] 骆抗先[1] 

机构地区：[1]广州第一军医大学南方医院感染内科,510515

出　　处：《肝脏》2003年第4期19-20,23,共3页Chinese Hepatology

摘　　要：目的　探讨乙型肝炎病毒 (HBV)C区热点变异S87G和 (或 )I97L对细胞毒T细胞表位形成的影响。方法　以我国C基因型HBVDNA参照序列为标准 (EMBL :Y1885 5 1885 8) ,在计算机预测I97L和 (或 )S87G变异对HLA A 0 2 0 1限制性表位影响的基础上 ,利用基因工程制备的HLA A 0 2 0 1轻链、重链多肽在体外只能与相应表位短肽形成稳定复合物的特点 ,对预测到的可疑表位肽段进行验证。结果　I97L时 ,肽段HBcAg 96 10 5 (KLRQLLWFHI)的DC50比正常 (KIRQLLWFHI)时大 5倍以上 ;S87G无影响 ;I97L、S87G没有协同作用。人工合成该短肽在体外不能与HLA A 0 2 0 1轻、重链多肽形成稳定复合物。结论　HBV/C基因I97L和 (或 )S87G变异时 ,没有新的HLA A 0 2 0 1限制表位产生。Objective To study the influence of hot spot mutations (S87G and/or I97L) of hepatitis B virus (HBV)/C gene on cytotoxic T lymphocyte (CTL) epitopes.Methods Human histocompatibility leukocyte antigen (HLA)-A*0201 binding prediction and motif database were downloaded from http://www-bimas.dcrt.nih.gov/and http://www.syfpeithi.de/, and consensus sequence of HBV/C gene from GenBank (EMBL:Y18855-18858). The ability of the predicted HLA-A*0201 restriction epitopes to form reconstituted complex in vitro was examined by the HLA-A*0201-peptide complexes. The extent of reconsititution was analyzed by gel filtration HPLC with monitoring absorbance at 280nm.Results I97L led to more than 5 times increase in DC 50(estimate of half time dissociation of a molecule containing this subsequence) of predicted CTL epitope to HLA-A*0201(HBcAg96-105,KLRQLLWFHI). But the peptide was not able to restitute with peptides of light chain and heavy chain of HLA-A*0201. No synergistic effect was found between I97L and S87G. Conclusion No new CTL epitopes to HLA-A*0201 are found at S87G and/or I97L.

关 键 词：HLA-肽复合物 HBV C区 基因变异 HLA-A2 限制性表位 细胞毒T细胞 乙型肝炎病毒 

分 类 号：R346[医药卫生—基础医学]