Wentworth P A, Sette A, Celis E, Sidney J, Southwood S, Crimi C, Stitely S, Keogh E, Wong N C, Livingston B, Alazard D, Vitiello A, Grey H M, Chisari F V, Chesnut R W, Fikes J
Cytel Corporation, San Diego, CA 92121, USA.
Int Immunol. 1996 May;8(5):651-9. doi: 10.1093/intimm/8.5.651.
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 immunogenicity in vitro in human primary CTL cultures and in vivo by direct immunization of HLA-A2.1/Kb transgenic 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.
我们聚焦于丙型肝炎病毒（HCV）基因组的保守区域，以鉴定含有HLA I类结合基序并与相应纯化的HLA分子高亲和力结合的病毒肽。因此，我们在HCV中鉴定出31个候选表位，它们有可能被HLA - A1、A2.1、A3、A11或A24限制性细胞毒性T淋巴细胞（CTL）识别。测试了12个与HLA - A2.1高亲和力或中等亲和力结合的保守肽在人原代CTL培养物中的体外免疫原性，以及通过直接免疫HLA - A2.1/Kb转基因小鼠进行体内免疫原性测试。6个HLA - A2.1限制性CTL表位在这两个系统中均具有免疫原性。这些肽表位中至少有三个被内源性加工并呈递给CTL识别。总体而言，这些数据说明了这种方法在开发病毒特异性肽基疫苗方面的价值。
