Ulivieri Cristina, Citro Alessandra, Ivaldi Federico, Mascolo Dina, Ghittoni Raffaella, Fanigliulo Daniela, Manca Fabrizio, Baldari Cosima Tatiana, Li Pira Giuseppina, Del Pozzo Giovanna
Department of Evolutionary Biology, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Immunol Lett. 2008 Aug 15;119(1-2):62-70. doi: 10.1016/j.imlet.2008.04.004. Epub 2008 May 19.
Several efforts have been invested in the identification of CTL and Th epitopes, as well as in the characterization of their immunodominance and MHC restriction, for the generation of a peptide-based HCMV vaccine. Small synthetic peptides are, however, poor antigens and carrier proteins are important for improving the efficacy of synthetic peptide vaccines. Recombinant bacteriophages appear as promising tools in the design of subunit vaccines. To investigate the antigenicity of peptides carried by recombinant bacteriophages we displayed different HCMV MHCII restricted peptides on the capsid of filamentous bacteriophage (fd) and found that hybrid bacteriophages are processed by human APC and activate HCMV-specific CD4 T-cells. Furthermore we constructed a reporter T-cell hybridoma expressing a chimeric TCR comprising murine alphabeta constant regions and human variable regions specific for the HLA-A2 restricted immunodominant NLV peptide of HCMV. Using the filamentous bacteriophage as an epitope carrier, we detected a more robust and long lasting response of the reporter T-cell hybridoma compared to peptide stimulation. Our results show a general enhancement of T-cell responses when antigenic peptides are carried by phages.
为了开发基于肽的人巨细胞病毒（HCMV）疫苗，人们在鉴定细胞毒性T淋巴细胞（CTL）和辅助性T细胞（Th）表位以及表征它们的免疫显性和主要组织相容性复合体（MHC）限制性方面投入了多项努力。然而，小的合成肽是较差的抗原，载体蛋白对于提高合成肽疫苗的效力很重要。重组噬菌体似乎是亚单位疫苗设计中很有前景的工具。为了研究重组噬菌体携带的肽的抗原性，我们在丝状噬菌体（fd）的衣壳上展示了不同的HCMV MHCII限制性肽，发现杂交噬菌体可被人抗原呈递细胞（APC）加工处理并激活HCMV特异性CD4 T细胞。此外，我们构建了一个报告T细胞杂交瘤，其表达一种嵌合T细胞受体（TCR），该受体包含鼠αβ恒定区和对HCMV的HLA - A2限制性免疫显性NLV肽具有特异性的人可变区。使用丝状噬菌体作为表位载体，我们检测到与肽刺激相比，报告T细胞杂交瘤的反应更强且更持久。我们的结果表明，当抗原肽由噬菌体携带时，T细胞反应普遍增强。
