Gaubin Muriel, Fanutti Cristina, Mishal Zohar, Durrbach Antoine, De Berardinis Piergiuseppe, Sartorius Rossella, Del Pozzo Giovanna, Guardiola John, Perham Richard N, Piatier-Tonneau Dominique
Génomique Fonctionnelle et Biologie Systémique en Santé, Centre National de la Recherche Scientifique, Villejuif, France.
DNA Cell Biol. 2003 Jan;22(1):11-8. doi: 10.1089/104454903321112451.
Virions of filamentous bacteriophage fd are capable of displaying multiple copies of peptide epitopes and generating powerful immune responses to them. To investigate the antigen processing mechanisms in human B cell lines used as antigen presenting cells, the major coat protein (pVIII) in intact virions was fluorescently labeled, and its localization in various intracellular compartments was followed using confocal microscopy. We show that the virions were taken up and processed to yield peptides that reach both the major histocompatibility complex (MHC) class II compartment and the endoplasmic reticulum. Moreover, when exposed to bacteriophages displaying a cytotoxic T lymphocyte (CTL) epitope from the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1), B cells were lysed by specific cytotoxic lymphocytes. This confirms that filamentous bacteriophage virions are capable of being taken up and processed efficiently by MHC class I and class II pathways, even in nonprofessional antigen presenting cells. These remarkable features explain, at least in part, the unexpected ability of virions displaying foreign T-cell epitopes to prime strong T-helper-dependent CTL responses. These findings have important implications for the development of peptide-based vaccines, using filamentous bacteriophage virions as scaffolds.
丝状噬菌体fd的病毒粒子能够展示多个拷贝的肽表位，并对其产生强大的免疫反应。为了研究用作抗原呈递细胞的人B细胞系中的抗原加工机制，对完整病毒粒子中的主要衣壳蛋白（pVIII）进行荧光标记，并使用共聚焦显微镜追踪其在各种细胞内区室中的定位。我们发现，病毒粒子被摄取并加工，产生的肽可到达主要组织相容性复合体（MHC）II类区室和内质网。此外，当暴露于展示来自人类免疫缺陷病毒1型（HIV-1）逆转录酶的细胞毒性T淋巴细胞（CTL）表位的噬菌体时，B细胞会被特异性细胞毒性淋巴细胞裂解。这证实了丝状噬菌体病毒粒子即使在非专职抗原呈递细胞中也能够通过MHC I类和II类途径被有效摄取和加工。这些显著特征至少部分解释了展示外源T细胞表位的病毒粒子引发强烈的T辅助细胞依赖性CTL反应的意外能力。这些发现对于以丝状噬菌体病毒粒子为支架开发基于肽的疫苗具有重要意义。
