中华皮肤科杂志 ›› 2005, Vol. 38 ›› Issue (6): 371-373.

• 论著 • 上一篇    下一篇

人乳头瘤病毒16E749-57的分子修饰与鉴定

徐云升1, 郝飞1, 郝进1, 杨希川1, 杨卫兵2   

  1. 1. 第三军医大学西南医院皮肤科 重庆 400038;
    2. 解放军第181医院皮肤科 重庆 400038
  • 收稿日期:2004-07-26 出版日期:2005-06-15 发布日期:2005-06-15
  • 通讯作者: 郝飞,E-mail:haofei@mail.tmmui.com.cn E-mail:haofei@mail.tmmui.com.cn
  • 基金资助:
    国家自然科学基金资助项目(30070698)

Molecular Modification and Identification of HPV16E749-57

XU Yun-sheng1, HAO Fei1, HAO Jin1, YANG Xi-chuan1, YANG Wei-bing2   

  1. Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
  • Received:2004-07-26 Online:2005-06-15 Published:2005-06-15

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摘要： 目的 对人乳头瘤病毒(HPV)16型E7抗原的人白细胞抗原A2分子限制性细胞毒性T细胞表位HPV16E749-57进行氨基酸置换修饰,并鉴定修饰表位。方法 运用量化模体方案对置换后的多肽与人白细胞抗原A2分子的结合系数进行比较,以分子模拟方法确定合成序列,采用标准Fmoc方案进行合成与纯化多肽以及乳酸脱氢酶释放法检测特异性细胞毒性T细胞诱导活性。结果 修饰多肽符合人白细胞抗原A2分子限制性细胞毒性T细胞的表位要求,9肽RLHYNIVTF具有特异性细胞毒性T细胞诱导活性。结论 修饰表位(氨基酸序列RLHYNIVTF)具有更好的结合力和较强的抗原性,可以代替原有序列E749-57(氨基酸序列RAHYNIVTF)作为人乳头瘤病毒感染治疗性肽疫苗分子设计的候选表位。

关键词: 氨基酸特征修饰, E7抗原, 表位,T淋巴细胞, 乳头状瘤病毒,人

Abstract: Objective To introduce the aminoacid substitution for HP V16E749-57(HLA-A2-restricted CTL epitope) and to identify the novel epitopes.Methods Quantitative method was used to evaluate the affinity of the substituted peptides.To determine the peptide candidates to be synthesized and identified,the molecular models of the HLA-A2-peptide complex and CTL epitope candidates bound to the HLA-A2 molecule were established by computer molecular modeling.Peptides were synthesized and purified with standard Fmoc assay,lactate dehydrogen ase (LDH) release assay was used to determine their abilities of inducing the generation of specific CTLs. Results Modified peptidesmet the requirements of H LA-A2-restricted CTL epitopes.Peptide RLHYNIVTF had the abilitiy of inducing the generation of specific CTLs. Conclusions Compared with HPV17E749-57 the modified peptide RLHYNIVTF has a higher antigenicity and affinity to HLA-A2.So,peptide RLHYNIVTF maybe used as one of the HLA-A2-restricted candidate epitopes,instead of HPV17E749-57,for peptide vaccine in the treatment of HPV infection.

Key words: Papillomavirus, human, Epitopes, T-lymphocyte, Amino acid motifs, E7 antigen