Partidos C D, Vohra P, Steward M W
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, UK.
Immunology. 1996 Feb;87(2):179-85. doi: 10.1046/j.1365-2567.1996.462527.x.
We have investigated the structural requirements for the induction of cytotoxic T-cell responses (CTL) in vivo after intranasal immunization with an immunodominant CTL epitope from the nucleoprotein of measles virus (MV). For the induction of CTL responses, covalent linkage of the CTL epitope to a helper T-cell epitope was required and the orientation of the epitopes influenced the immunogenicity of the CTL epitope. The presence of two copies as compared with one copy of a T-helper epitope, rendered the CTL epitope more immunogenic and resulted in the in vivo induction of MV-specific CTLs without the need for an adjuvant. The role of CTL responses to this epitope in protection after intranasal administration was evaluated in a mouse model against challenge with a neuroadapted strain of MV. Although a decreased mortality in the peptide immunized compared with that in unimmunized mice was observed, the protection achieved was not significant. These findings highlight the importance of the rational design of synthetic immunogens for the induction of CTL responses and the potential of the intranasal route for immunization.
我们研究了用麻疹病毒（MV）核蛋白的免疫显性细胞毒性T细胞（CTL）表位经鼻内免疫后，在体内诱导CTL反应的结构要求。为诱导CTL反应，CTL表位与辅助性T细胞表位的共价连接是必需的，且表位的方向影响CTL表位的免疫原性。与一个辅助性T细胞表位拷贝相比，两个拷贝的存在使CTL表位更具免疫原性，并导致在无需佐剂的情况下在体内诱导出MV特异性CTL。在针对神经适应株MV攻击的小鼠模型中，评估了针对该表位的CTL反应在经鼻给药后保护作用中的作用。虽然观察到与未免疫小鼠相比，肽免疫小鼠的死亡率有所降低，但所实现的保护并不显著。这些发现突出了合理设计合成免疫原以诱导CTL反应的重要性以及经鼻免疫途径的潜力。
