Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome.
Identification of A2-restricted hepatitis C virus-specific cytotoxic T lymphocyte epitopes from conserved regions of the viral genome.
复制标题
从病毒基因组的保守区域鉴定 A2 限制性丙型肝炎病毒特异性细胞毒性 T 淋巴细胞表位。
DOI：
10.1093/intimm/8.5.651
复制
发表时间：
1996
影响因子：
4.4
通讯作者：
Fikes,J
中科院分区：
文献类型：
--
作者：
Wentworth,PA;Sette,A;Celis,E;Sidney,J;Southwood,S;Crimi,C;Stitely,S;Keogh,E;Wong,NC;Livingston,B;Alazard,D;Vitiello,A;Grey,HM;Chisari,FV;Chesnut,RW;Fikes,J
我们专注于丙型肝炎病毒 (HCV) 基因组的保守区域，以鉴定包含 HLA I 类结合基序并以高亲和力与相应的纯化 HLA 分子结合的病毒肽。因此，我们在 HCV 中鉴定出了 31 个候选表位，这些表位有可能被 HLA-A1、A2.1、A3、A11 或 A24 限制性细胞毒性 T 淋巴细胞 (CTL) 识别。以高或中等亲和力结合 HLA-A2.1 的 12 种保守肽在人原代 CTL 培养物中进行了体外免疫原性测试，并通过直接免疫 HLA-A2.1/Kb 转基因小鼠进行了体内免疫原性测试。六个 HLA-A2.1 限制性 CTL 表位在两个系统中均具有免疫原性。这些肽表位中的至少三个经过内源加工并呈递用于 CTL 识别。总的来说，这些数据说明了这种方法对于开发病毒特异性、基于肽的疫苗的价值。
We have focused on conserved regions of the hepatitis C Virus (HCV) genome to identify viral peptides that contain HLA class I binding motifs and bind with high affinity to the corresponding purified HLA molecules. Accordingly, we have identified 31 candidate epitopes in the HCV that have the potential to be recognized by either HLA-A1-, A2.1-, A3-, A11- or A24-restricted cytotoxic T lymphocytes (CTL). Twelve conserved peptides that bind HLA-A2.1 with high or intermediate affinity were tested for immunogenicityin vitroin human primary CTL cultures andin vivoby direct immunization of HLA-A2.1/Kbtransgenic mice. Six HLA-A2.1-restricted CTL epitopes were immunogenic in both systems. At least three of these peptide epitopes were endogenously processed and presented for CTL recognition. Overall, these data illustrate the value of this approach for the development of virus-specific, peptide-based vaccines.