Morón Víctor Gabriel, Rueda Paloma, Sedlik Christine, Leclerc Claude
Unité de Biologie des Régulations Immunitaires, Institut National de la Santé et de la Recherche Médicale, E352, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
J Immunol. 2003 Sep 1;171(5):2242-50. doi: 10.4049/jimmunol.171.5.2242.
Recombinant parvovirus-like particles (PPV-VLPs) are particulate exogenous Ags that induce strong CTL response in the absence of adjuvant. In the present report to decipher the mechanisms responsible for CTL activation by such exogenous Ag, we analyzed ex vivo and in vitro the mechanisms of capture and processing of PPV-VLPs by dendritic cells (DCs). In vivo, PPV-VLPs are very efficiently captured by CD8alpha- and CD8alpha+ DCs and then localize in late endosomes of DCs. Macropinocytosis and lipid rafts participate in PPV-VLPs capture. Processing of PPV-VLPs does not depend upon recycling of MHC class I molecules, but requires vacuolar acidification as well as proteasome activity, TAP translocation, and neosynthesis of MHC class I molecules. This study therefore shows that in vivo DCs can cross-present PPV-VLPs using an endosome-to-cytosol processing pathway.
重组细小病毒样颗粒（PPV-VLPs）是颗粒状外源性抗原，在无佐剂的情况下可诱导强烈的细胞毒性T淋巴细胞（CTL）反应。在本报告中，为了解释此类外源性抗原激活CTL的机制，我们在体外和体内分析了树突状细胞（DCs）捕获和处理PPV-VLPs的机制。在体内，PPV-VLPs能被CD8α-和CD8α+ DCs高效捕获，然后定位在DCs的晚期内体中。巨胞饮作用和脂筏参与PPV-VLPs的捕获。PPV-VLPs的处理不依赖于MHC I类分子的循环，但需要液泡酸化以及蛋白酶体活性、抗原加工相关转运体（TAP）转运和MHC I类分子的重新合成。因此，本研究表明，在体内DCs可利用内体到胞质溶胶的处理途径交叉呈递PPV-VLPs。
