van Montfoort Nadine, Camps Marcel G, Khan Selina, Filippov Dmitri V, Weterings Jimmy J, Griffith Janice M, Geuze Hans J, van Hall Thorbald, Verbeek J Sjef, Melief Cornelis J, Ossendorp Ferry
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6730-5. doi: 10.1073/pnas.0900969106. Epub 2009 Apr 3.
Dendritic cells (DCs) are crucial for priming of naive CD8(+) T lymphocytes to exogenous antigens, so-called "cross-priming." We report that exogenous protein antigen can be conserved for several days in mature DCs, coinciding with strong cytotoxic T lymphocyte cross-priming potency in vivo. After MHC class I peptide elution, protein antigen-derived peptide presentation is efficiently restored, indicating the presence of an intracellular antigen depot. We characterized this depot as a lysosome-like organelle, distinct from MHC class II compartments and recently described early endosomal compartments that allow acute antigen presentation in MHC class I. The storage compartments we report here facilitate continuous supply of MHC class I ligands. This mechanism ensures sustained cross-presentation by DCs, despite the short-lived expression of MHC class I-peptide complexes at the cell surface.
树突状细胞(DCs)对于将初始CD8(+) T淋巴细胞致敏于外源性抗原(即所谓的“交叉致敏”)至关重要。我们报告称,外源性蛋白质抗原可在成熟DCs中保存数天,这与体内强大的细胞毒性T淋巴细胞交叉致敏能力相一致。在MHC I类肽洗脱后,蛋白质抗原衍生肽的呈递得以有效恢复,表明存在细胞内抗原库。我们将此抗原库鉴定为一种溶酶体样细胞器,它不同于MHC II类区室以及最近描述的允许MHC I类急性抗原呈递的早期内体区室。我们在此报告的储存区室有助于持续供应MHC I类配体。尽管MHC I类 - 肽复合物在细胞表面的表达短暂,但这种机制确保了DCs持续的交叉呈递。