Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065-6399, USA.
Eur J Immunol. 2010 Jan;40(1):36-46. doi: 10.1002/eji.200939748.
DC present exogenous proteins to MHC class I-restricted CD8+ T cells. This function does not require endogenous antigen synthesis within DC, providing the potential to elicit CD8+ T-cell responses to immune complexes, inactivated microbes, dying cells, and proteins such as OVA. In mice, the CD8+ or DEC-205+ DC are specialized for cross-presentation, and this subset can be increased 10-fold in numbers following Fms-like tyrosine kinase 3 ligand (Flt3L) treatment in vivo. Therefore, we studied cross-presentation by abundant Flt3L DC using HIV gag protein. When enriched by positive selection with anti-CD11c beads, cells from Flt3L mice are not only more abundant but are also more highly enriched in CD11chigh DC, particularly the DEC-205+ subset. DC cross-present HIV gag to primed CD8+ T cells, but when the antigen is delivered within an antibody to DEC-205 receptor, cross-presentation becomes 100-fold more efficient than non-targeted antigen. This finding requires gag to be engineered into anti-DEC antibody, not just mixed with antibody. Flt3L DC are a valuable tool to study cross-presentation, since their use overcomes the obstacle posed by the low number of cross-presenting DC in the steady state. These findings support future experiments to use Flt3L to enhance presentation of DC-targeted vaccines.
树突状细胞向 MHC Ⅰ类限制的 CD8+T 细胞呈递外源性蛋白。这种功能不需要树突状细胞内源性抗原的合成，为免疫复合物、失活的微生物、死亡的细胞和 OVA 等蛋白质引发 CD8+T 细胞反应提供了潜力。在小鼠中，CD8+或 DEC-205+树突状细胞专门进行交叉呈递，在体内用 Fms 样酪氨酸激酶 3 配体（Flt3L）处理后，这一亚群的数量可增加 10 倍。因此，我们使用 HIV gag 蛋白研究了丰富的 Flt3L 树突状细胞的交叉呈递。用抗 CD11c 珠进行阳性选择富集后，Flt3L 小鼠的细胞不仅数量更多，而且 CD11chigh 树突状细胞，特别是 DEC-205+亚群的富集程度更高。树突状细胞将 HIV gag 交叉呈递给已被激活的 CD8+T 细胞，但当抗原被递呈到 DEC-205 受体的抗体中时，交叉呈递的效率比非靶向抗原高 100 倍。这一发现要求 gag 被构建到抗 DEC 抗体中，而不仅仅是与抗体混合。Flt3L 树突状细胞是研究交叉呈递的有价值的工具，因为它们的使用克服了在稳定状态下交叉呈递树突状细胞数量低的障碍。这些发现支持未来使用 Flt3L 增强针对树突状细胞的疫苗呈递的实验。
