Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.
Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance.
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DOI：
10.1084/jem.20021598
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发表时间：
2002-12-16
影响因子：
15.3
通讯作者：
Steinman, RM
中科院分区：
文献类型：
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作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
为了鉴定允许树突状细胞（DC）在体内捕获和呈递主要组织相容性复合体（MHC）I类产物上的抗原的内吞受体，我们评估了DEC-205，其在淋巴组织中的DC上丰富。当卵清蛋白（OVA）蛋白与单克隆αDEC-205抗体化学偶联时，由CD 11 c+淋巴结DC（而非CD 11 c −细胞）呈递给OVA特异性、CD 4+和CD 8 + T细胞。受体介导的介绍是至少400倍以上的效率比未缀合的卵清蛋白和MHC I类，DC表达抗原肽转运蛋白（TAP）转运。当皮下注射αDEC-205：OVA时，在4-48小时内在DC中（主要在注射部位引流的淋巴结中）鉴定出OVA蛋白。在体内，OVA蛋白被DC选择性地呈递给TCR转基因CD 8+细胞，同样比可溶性OVA有效至少400倍，并且以TAP依赖的方式。αDEC-205：OVA靶向稳态DC最初诱导了4-7个T细胞分裂周期，但随后T细胞被删除，小鼠对完全弗氏佐剂中的OVA再激发特异性无反应。相比之下，通过CD 40同时递送DC成熟刺激物以及αDEC-205：OVA诱导了强免疫。CD 8 + T细胞在激动性α CD 40抗体存在下产生大量白细胞介素2和干扰素γ，在体内获得细胞溶解功能，大量迁移到肺，并对OVA再激发产生强烈反应。因此，DEC-205为DC提供了一种有效的基于受体的机制，以在体内加工用于MHC I类呈递的蛋白质，从而导致DC成熟后的稳态耐受和免疫。
To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
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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
影响因子：
4.4
作者：
Kurts, C;Cannarile, M;Brocker, T
通讯作者：
Brocker, T
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
DOI：
10.1084/jem.191.3.435
发表时间：
2000-02-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang FP;Platt N;Wykes M;Major JR;Powell TJ;Jenkins CD;MacPherson GG
通讯作者：
MacPherson GG
影响因子：
15.3
作者：
Dhodapkar, KM;Krasovsky, J;Dhodapkar, MV
通讯作者：
Dhodapkar, MV