Fayolle C, Abdel-Motal U M, Berg L, Deriaud E, Jondal M, Leclerc C
Unitè de Biologie des Regulations Immunitaircs, Institut Pasteur Paris, France.
Immunology. 1996 Sep;89(1):41-5. doi: 10.1046/j.1365-2567.1996.d01-704.x.
In several experimental models, synthetic peptides were shown to activate efficiently cytotoxic T-lymphocyte (CTL) responses and therefore represent an attractive strategy to develop new vaccines. However, the mechanisms by which they induce CTL responses are not yet fully understood. Several studies using 15 16-mer peptides previously demonstrated that CD4 helper T cells are required to induce optimal CTL responses with synthetic peptides. However, recently it was suggested that shorter 8 12-mer peptides could have an increased in vivo immunogenicity. In the present study, we therefore investigated if such optimal-length peptides still require CD4+ T-cell help to activate CTL responses. To address this question three synthetic peptides containing different viral CTL epitopes were injected into mice depleted of CD4+ or CD8+ T cells using specific monoclonal antibodies or into mice genetically deficient in those T-cell populations. Our results clearly established that activation of CTL responses by those short optimal peptides does not require CD4+ T-cell help and therefore suggested that high-density binding of peptides to major histocompatibility complex class I molecules on the surface of antigen-presenting cells is required for direct activation of CD8+ T cells, independently of CD4+ T-cell help.
在多个实验模型中，合成肽已被证明能有效激活细胞毒性T淋巴细胞（CTL）反应，因此是开发新型疫苗的一个有吸引力的策略。然而，它们诱导CTL反应的机制尚未完全清楚。此前多项使用15至16聚体肽的研究表明，需要CD4辅助性T细胞来诱导合成肽产生最佳的CTL反应。然而，最近有人提出，较短的8至12聚体肽可能具有更高的体内免疫原性。因此，在本研究中，我们调查了此类最佳长度的肽是否仍需要CD4+ T细胞的辅助来激活CTL反应。为解决这个问题，我们使用特异性单克隆抗体将三种含有不同病毒CTL表位的合成肽注射到耗尽CD4+或CD8+ T细胞的小鼠体内，或注射到这些T细胞群体存在基因缺陷的小鼠体内。我们的结果清楚地表明，这些短的最佳肽激活CTL反应不需要CD4+ T细胞的辅助，因此表明肽与抗原呈递细胞表面的主要组织相容性复合体I类分子的高密度结合是直接激活CD8+ T细胞所必需的，而无需CD4+ T细胞的辅助。
