A novel modular antigen delivery system for immuno targeting of human 6-sulfo LacNAc-positive blood dendritic cells (SlanDCs).
A novel modular antigen delivery system for immuno targeting of human 6-sulfo LacNAc-positive blood dendritic cells (SlanDCs).
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DOI：
10.1371/journal.pone.0016315
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发表时间：
2011-01-21
期刊：
影响因子：
3.7
通讯作者：
Bachmann M
中科院分区：
文献类型：
--
作者：
Bippes CC;Feldmann A;Stamova S;Cartellieri M;Schwarzer A;Wehner R;Schmitz M;Rieber EP;Zhao S;Schäkel K;Temme A;Scofield RH;Kurien BT;Bartsch H;Bachmann M
在此之前，我们发现了人类血液树突状细胞中一个主要的髓系前炎症亚群，我们称之为slanDC(例如Schäkel等人)。(2006)豁免24,767-777)。SLAN表位是P-选择素糖蛋白配体-1(PSGL-1)的O-连接糖链修饰(6-Sulo LacNAc，SLAN)。由于slanDC可以诱导新抗原特异性的CD4+T细胞和肿瘤反应性CD8+细胞毒性T细胞，因此它们有望成为体内运送抗原进行疫苗接种的靶点。然而，到目前为止，还没有将抗原输送到slanDC的工具。此外，尚不清楚通过slan表位传递的抗原是否能够被slanDC提取、适当处理并呈递给T细胞。从目前可用的十价抗slan IgM单抗中制备单链片段变量，但不能与slanDC结合。因此，我们开发了一种新型的多价抗slanDC支架，该支架由两部分组成：(I)单链双特异性重组双功能双功能重组双功能双功能重组双功能重组双功能通过这种scBsDb/抗原支架将破伤风毒素衍生抗原运送到slanDC，使我们能够召回自体破伤风特异性记忆T细胞。综上所述，我们的数据表明：(I)slan表位可用于向这类人类特异性DC运送抗原，以及(Ii)slan表位结合的抗原可被slanDC提取、处理并呈递给T细胞。因此，我们的新型模块化支架系统可能对人类疫苗的开发有用。
Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells. Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells. In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines.
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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：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
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：
15.9
作者：
GAITHER, KK;FOX, OF;HARLEY, JB
通讯作者：
HARLEY, JB
DOI：
10.1073/pnas.0802644105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Mukhopadhaya, Arunika;Hanafusa, Tadashi;DiLorenzo, Teresa P.
通讯作者：
DiLorenzo, Teresa P.