In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination.
In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination.
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DOI：
10.1084/jem.20032220
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发表时间：
2004-03-15
影响因子：
15.3
通讯作者：
Steinman, RM
中科院分区：
文献类型：
--
作者：
Bonifaz, LC;Bonnyay, DP;Charalambous, A;Darguste, DI;Fujii, SI;Soares, H;Brimnes, MK;Moltedo, B;Moran, TM;Steinman, RM
预防和治疗流行的传染病和肿瘤应受益于抗原特异性T细胞免疫诱导的改善。为了评估抗原靶向树突状细胞以提高免疫力的潜力，我们将卵清蛋白蛋白掺入DEC-205受体的单克隆抗体中，DEC-205受体是淋巴组织中这些细胞上丰富的内吞受体。同时注射激动性α-CD 40抗体使树突状细胞成熟。我们发现，一个单一的低剂量的抗体结合的卵清蛋白启动免疫从幼稚的CD 4+和CD 8 + T细胞库。出乎意料的是，皮下给予αDEC-205抗原缀合物，靶向树突状细胞全身和长时间，卵清蛋白肽呈递在MHC I类2周。这与相对于其他形式的抗原递送更强的CD 8 + T细胞介导的免疫相关，即使后者以高出一千倍的剂量给予。同时，小鼠对建立的快速生长的肿瘤和粘膜部位的病毒感染表现出增强的抵抗力。通过更好地利用成熟树突状细胞的免疫功能，通过DEC-205受体的抗体介导的抗原靶向增加了T细胞免疫的疫苗接种效率，包括疾病模型中的全身和粘膜抗性。
The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic α-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the αDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell–mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models.
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DOI：
10.1083/jcb.151.3.673
发表时间：
2000-10-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mahnke K;Guo M;Lee S;Sepulveda H;Swain SL;Nussenzweig M;Steinman RM
通讯作者：
Steinman RM
影响因子：
64.8
作者：
Houde, M;Bertholet, S;Desjardins, M
通讯作者：
Desjardins, M
影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC