期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：17
页码：5461-5466
DOI：10.1073/pnas.1423356112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceAlthough we know much about the molecular mechanisms of cross-presentation, its actual contribution to cytotoxic T cell (CTL) immunity under physiological conditions in vivo is still unclear. Cross-presentation is based on the idea that dendritic cells (DCs) are the only professional antigen-presenting cells able to prime naive T cells. If DCs are not directly infected, they must take up antigen and present it indirectly. However, recent evidence suggests that other cells also may be involved in T cell priming, which probably makes cross-presentation less central. This study shows that cross-priming DCs generate highly restricted CTL repertoires, biased to strong MHC I binding epitopes only. Furthermore, the presence of antigen in CD169+ macrophages is sufficient for generation of CTLs with broader repertoires. Dendritic cells (DCs) are considered the most potent antigen-presenting cells (APCs), which directly prime or cross-prime MHC I-restricted cytotoxic T cells (CTLs). However, recent evidence suggests the existence of other, as-yet unidentified APCs also able to prime T cells. To identify those APCs, we used adenoviral (rAd) vectors, which do not infect DCs but selectively accumulate in CD169+ macrophages (MPs). In mice that lack DCs, infection of CD169+ MPs was sufficient to prime CTLs specific for all epitopes tested. In contrast, CTL responses relying exclusively on cross-presenting DCs were biased to selected strong MHC I-binding peptides only. When both DCs and MPs were absent, no CTL responses could be elicited. Therefore, CD169+ MPs can be considered APCs that significantly contribute to CTL responses.
