Lu Lu, Zhu Yun, Diao Junchen, Wang Zuguang, Chen Ying-Hua
Laboratory of Immunology, Department of Biology and Institute of Biomedical Science, Tsinghua University, Protein Science Laboratory of the MOE, Beijing 100084, PR China.
Vaccine. 2008 Feb 6;26(6):845-52. doi: 10.1016/j.vaccine.2007.11.022. Epub 2007 Nov 29.
Previous studies have found the close correlation between epitope density and epitope-specific response, which have shown that high epitope density in a single recombinant protein molecule significantly enhances the humoral response and protective immunity. However, it has not been determined whether this kind of high epitope density could also significantly influence T cell response. Based on this, a series of recombinant DNA and proteins were designed and prepared. Each molecule consists of various copy numbers of the V3 CTL epitope on HIV-1 gp120 (one, two, four and eight copies). Our results show clearly that different V3-epitope densities in just one single DNA or protein molecules have respectively different effects on the number and activity of both primary and memory T cells. Interestingly, this effect is more complex than that on the B cells: epitope density in one plasmid or protein antigen affects the number, not the cytotoxic avidity, of primary CD8+ T cells, but affects both the number and cytotoxic avidity of memory CD8+ T cells. It indicates epitope density in the antigen is an important consideration to optimize T cell response induction and may facilitate the development of effective T cell-based anti-virus vaccines.
先前的研究发现表位密度与表位特异性反应之间存在密切关联,这些研究表明单个重组蛋白分子中的高表位密度可显著增强体液反应和保护性免疫。然而,尚未确定这种高表位密度是否也会显著影响T细胞反应。基于此,设计并制备了一系列重组DNA和蛋白质。每个分子由HIV-1 gp120上不同拷贝数的V3 CTL表位组成(一、二、四和八个拷贝)。我们的结果清楚地表明,仅一个DNA或蛋白质分子中不同的V3表位密度对初始T细胞和记忆T细胞的数量及活性分别具有不同的影响。有趣的是,这种影响比其对B细胞的影响更为复杂:一种质粒或蛋白质抗原中的表位密度影响初始CD8+ T细胞的数量,而非细胞毒性亲和力,但会影响记忆CD8+ T细胞的数量和细胞毒性亲和力。这表明抗原中的表位密度是优化T细胞反应诱导的一个重要考量因素,并且可能有助于开发有效的基于T细胞的抗病毒疫苗。