Sauzet J P, Gras-Masse H, Guillet J G, Gomard E
Laboratoire d'immunologie des interactions cellulaires et moléculaires, INSERM U152, Institut Cochin de Génétique Moléculaire, Paris, France.
Int Immunol. 1996 Apr;8(4):457-65. doi: 10.1093/intimm/8.4.457.
Free unmodified peptides are poor immunogens for cytotoxic T lymphocytes (CTL) in mice, unless they are injected with adjuvant. Although it is generally accepted that CD4+ Th cells are essential for CTL priming with peptides, it is not clear how long sequences devoid of any CD4 epitope, or strict CD8 epitopic sequences too short to be presented in a MHC class II-restricted fashion, can generate such responses. We thus have examined the extent to which the immunization protocol affects the need for a CD4 epitope. Since peptides are potentially important for vaccination, we also examined the duration of the CTL responses using a set of peptides that contained a CD4 epitope, or a CD8 epitope, or both epitopes in the same sequence, and compared immunization protocols previously found to induce CTL responses with peptides. The in vivo injection protocol had a marked effect, since the same CD8 sequence could generate a CTL response in a Th-dependent or Th-independent fashion, depending on the protocol used. The T cell help provided by natural CD4-CD8 sequences was inefficient in Th-dependent CTL priming and CTL generation required help from a stronger exogenous CD4 peptide. The peptides could be injected either as a single tandem CD8-CD4 peptide or as a mixture of two separate peptides. Th-independent CTL responses primed in other conditions proved to be as strong as Th-dependent responses, at least when the animals were killed shortly after the last injection. However, only CTL responses generated together with specific Th cells persisted for several months. Moreover, the efficacy of CTL persistence seemed to be correlated with the strength of the CD4 epitope for priming. This has important implications for the design of peptide vaccines.
游离的未修饰肽对小鼠细胞毒性T淋巴细胞（CTL）而言是较差的免疫原，除非与佐剂一起注射。虽然一般认为CD4⁺ Th细胞对于肽引发CTL至关重要，但尚不清楚缺乏任何CD4表位的长序列，或短到无法以MHC II类限制方式呈递的严格CD8表位序列，如何能产生此类反应。因此，我们研究了免疫方案在多大程度上影响对CD4表位的需求。由于肽对疫苗接种可能很重要，我们还使用一组在同一序列中包含CD4表位、CD8表位或两者皆有的肽，研究了CTL反应的持续时间，并比较了先前发现能诱导肽引发CTL反应的免疫方案。体内注射方案有显著影响，因为相同的CD8序列可以以依赖Th或不依赖Th的方式产生CTL反应，这取决于所使用的方案。天然CD4 - CD8序列提供的T细胞辅助在依赖Th的CTL引发中效率低下，CTL的产生需要更强的外源性CD4肽的辅助。肽可以作为单个串联的CD8 - CD4肽注射，也可以作为两种单独肽的混合物注射。在其他条件下引发的不依赖Th的CTL反应被证明与依赖Th的反应一样强烈，至少在最后一次注射后不久处死动物时是这样。然而，只有与特定Th细胞一起产生的CTL反应持续数月。此外，CTL持续存在的效力似乎与引发反应的CD4表位的强度相关。这对肽疫苗的设计具有重要意义。
