Fusion Proteins for Versatile Antigen Targeting to Cell Surface Receptors Reveal Differential Capacity to Prime Immune Responses
Fusion Proteins for Versatile Antigen Targeting to Cell Surface Receptors Reveal Differential Capacity to Prime Immune Responses
复制标题
DOI：
10.4049/jimmunol.0902555
复制
发表时间：
2010-06-15
影响因子：
4.4
通讯作者：
van Endert, Peter
中科院分区：
文献类型：
--
作者：
Kratzer, Roland;Mauvais, Francois-Xavier;van Endert, Peter
将蛋白质靶向APC是引发适应性免疫应答的有吸引力的策略。然而，靶向受体的选择与反应的质量和数量之间的关系仍然知之甚少。我们描述了一种策略，包括疏水蛋白作为可溶性融合蛋白，蛋白酶体依赖的MHC I类限制性交叉呈递，并形成稳定的复合物与各种各样的靶向抗体的抗原表达。皮下注射后免疫后，这些复合物最初被CD 169（+）淋巴结被膜下窦巨噬细胞摄取。在OVA模型系统中，受体靶向抗原复合物在体外和体内引发特异性T和B细胞应答的效率比单独的Ag高至少100倍。10种靶向受体的比较使我们能够建立关于CD 8（+）T细胞应答的引发的排名，并且证明了关于CD 8（+）和CD 4（+）T细胞亚群和B细胞引发的相对功效的显著差异。所述融合蛋白应有助于开发在耐受化或疫苗接种的背景下靶向递送蛋白Ag的优化策略。免疫学杂志，2010，184：6855-6864。
Targeting of proteins to APCs is an attractive strategy for eliciting adaptive immune responses. However, the relationship between the choice of the targeted receptor and the quality and quantity of responses remains poorly understood. We describe a strategy for expression of Ags including hydrophobic proteins as soluble fusion proteins that are optimized for proteasome-dependent MHC class I-restricted cross-presentation and form stable complexes with a wide variety of targeting Abs. Upon s.c. immunization, these complexes were initially taken up by CD169(+) lymph node subcapsular sinus macrophages. In the OVA model system, receptor-targeted antigenic complexes primed specific T and B cell responses in vitro and in vivo at least 100-fold more efficiently than Ag alone. Comparison of 10 targeting receptors allowed us to establish a ranking with respect to priming of CD8(+) T cell responses and demonstrated striking differences with respect to the relative efficacy of CD8(+) and CD4(+) T cell subset and B cell priming. The described fusion proteins should help in developing optimized strategies for targeted delivery of protein Ags in the context of tolerization or vaccination. The Journal of Immunology, 2010, 184: 6855-6864.