Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus
Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus
复制标题
DOI：
10.1099/vir.0.80219-0
复制
发表时间：
2004-11-01
影响因子：
3.8
通讯作者：
Del Val, M
中科院分区：
文献类型：
--
作者：
Johnstone, C;de León, P;Del Val, M
人类呼吸道合胞病毒(RSV)是引起儿童和老年人呼吸道感染的主要原因。RSV融合(F)糖蛋白长期以来一直被认为是一种候选疫苗，因为它能引起细胞毒性T淋巴细胞(CTL)和抗体反应。在RSV A2株的F蛋白中发现了两个小鼠H-2K(D)限制性CTL表位(F85-93和F92-106)。以人RSV长毒株持续感染的BCH4成纤维细胞为刺激物，建立了F-特异性CTL株，发现该株只有F85-93表位是保守的。基于Motif的表位预测程序和在重组痘苗病毒中编码的F2链缺失的F蛋白使得能够在长株F249-258中鉴定出一个新的表位，K-d以9-聚体(TYMLTNSEL)或10-聚体(TYMLTNSELL)的形式呈现。结果表明，该10-聚体可能是一种自然加工的包含型K-d配体。对RSV Long F蛋白表位F85-93和F249-258的CD8(+)T淋巴细胞反应在体外多特异性CTL株和体内对表达整个F蛋白的重组痘苗病毒的二次反应中被发现强烈偏向于F85-93。然而，在体内没有观察到2004年7月21日接受F85-93和F249-258表位的CD8(+)T淋巴细胞反应的等级。
Human respiratory syncytial virus (RSV) is a major cause of respiratory infection in children and in the elderly. The RSV fusion (F) glycoprotein has long been recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and antibody responses. Two murine H-2K(d)-restricted CTL epitopes (F85-93 and F92-106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines using BCH4 fibroblasts that are persistently infected with the Long strain of human RSV as stimulators were generated, and it was found that in this strain only the F85-93 epitope is conserved. Motif based epitope prediction programs and an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled identification of a new epitope in the Long strain, F249-258, which is presented by K-d as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results suggest that the 10-mer might be a naturally processed enclogenous K-d ligand. The CD8(+) T-lymphocyte responses to epitopes F85-93 and F249-258 present in the F protein of RSV Long were found to be strongly skewed to F85-93 in in vitro multispecific CTL lines and in vivo during a secondary response to a recombinant vaccinia virus Received 23 April 2004 that expresses the entire F protein. However, no hierarchy in CD8(+) T-lymphocyte responses Accepted 21 July 2004 to F85-93 and F249-258 epitopes was observed in vivo during a primary response.