You Z, Huang X F, Hester J, Rollins L, Rooney C, Chen S Y
Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
J Immunol. 2000 Oct 15;165(8):4581-91. doi: 10.4049/jimmunol.165.8.4581.
Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.
高效的抗原呈递对于诱导有效的细胞免疫和体液免疫反应至关重要。因此，当前免疫治疗和疫苗开发的一个核心目标是增强抗原呈递以诱导强大而广泛的免疫反应。在此，通过转导树突状细胞（DCs）以产生一种抗原作为外源性抗原进行呈递，从而开发出一种新型的抗原呈递策略，以有效诱导体液免疫和细胞免疫。该策略的原理通过对DCs进行基因改造得以阐明，使其分泌与细胞结合域融合的乙型肝炎病毒模型抗原，并在受体介导的内化后将融合抗原作为外源性抗原进行加工，用于MHC I类和II类呈递。在小鼠模型中，转导的DCs诱导了强烈的抗原特异性CD4(+)辅助性T细胞和CD8(+)细胞毒性T细胞以及B细胞反应。因此，这种新型策略利用受体介导的内化过程有效诱导适应性免疫的所有分支，可能为开发强效疫苗和免疫疗法提供有力手段。
