Genentech, South San Francisco, CA 94080, USA.
J Exp Med. 2013 May 6;210(5):1049-63. doi: 10.1084/jem.20121251. Epub 2013 Apr 8.
Human BDCA3(+) dendritic cells (DCs), the proposed equivalent to mouse CD8α(+) DCs, are widely thought to cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for cross presentation or a generally enhanced ability to present antigens on MHCI. We compared presentation by BDCA3(+) DCs with BDCA1(+) DCs using a quantitative approach whereby antigens were targeted to distinct intracellular compartments by receptor-mediated internalization. As expected, BDCA3(+) DCs were superior at cross presentation of antigens delivered to late endosomes and lysosomes by uptake of anti-DEC205 antibody conjugated to antigen. This difference may reflect a greater efficiency of antigen escape from BDCA3(+) DC lysosomes. In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1(+) DCs were as efficient at cross presentation as BDCA3(+) DCs. Because BDCA3(+) DCs and BDCA1(+) DCs were also equivalent at presenting peptides and endogenously synthesized antigens, BDCA3(+) DCs are not likely to possess mechanisms for cross presentation that are specific to this subset. Thus, multiple DC populations may be comparably effective at presenting exogenous antigens to CD8(+) T cells as long as the antigen is delivered to early endocytic compartments.
人类 BDCA3(+)树突状细胞 (DC)，被认为相当于小鼠 CD8α(+)DC，被广泛认为比其他 DC 群体更有效地交叉呈递 MHC Ⅰ类 (MHCⅠ) 分子上的抗原。如果这是真的，目前尚不清楚这是否反映了交叉呈递的专业化，还是普遍增强了在 MHCⅠ上呈递抗原的能力。我们通过受体介导的内化将抗原靶向不同的细胞内区室的定量方法比较了 BDCA3(+)DC 和 BDCA1(+)DC 的呈递。正如预期的那样，BDCA3(+)DC 在外源抗原通过与抗原结合的抗 DEC205 抗体摄取到晚期内体和溶酶体中时，在交叉呈递抗原方面表现出色。这种差异可能反映了 BDCA3(+)DC 溶酶体中抗原逃逸的效率更高。相比之下，如果抗原通过 CD40 或 CD11c 递送至早期内体，BDCA1(+)DC 在交叉呈递方面与 BDCA3(+)DC 一样有效。由于 BDCA3(+)DC 和 BDCA1(+)DC 在呈递肽和内源性合成抗原方面也等效，BDCA3(+)DC 不太可能具有针对该亚群的特定交叉呈递机制。因此，只要抗原递送至早期内吞区室，多个 DC 群体可能同样有效地将外源性抗原呈递给 CD8(+)T 细胞。
