Brewer James M, Pollock Kevin G J, Tetley Laurence, Russell David G
Division of Immunology, Infection, and Inflammation, University of Glasgow, Western Infirmary, Glasgow G11 6NT, Scotland, UK.
J Immunol. 2004 Nov 15;173(10):6143-50. doi: 10.4049/jimmunol.173.10.6143.
Although it is accepted that particulate Ags are more immunogenic than soluble Ags in vivo, it is unclear whether this effect can be explained solely through enhanced uptake by APCs. In this study we demonstrate that vesicle size modulated the efficiency of Ag presentation by murine macrophages and that this effect was accompanied by a profound change in trafficking of Ag. Ag prepared in large particles (560 nm) was delivered into early endosome-like, immature phagosomes, whereas smaller vesicles (155 nm) and soluble Ags localized rapidly to late endosomes/lysosomes. However, peptide/class II complexes could be detected in both compartments. Phagosomes formed on uptake of large vesicles recruit Ag-processing apparatus while retaining the characteristics of early endosomes. In contrast, smaller vesicles bypassed this compartment, appeared to go more rapidly to lysosomal compartments, and exhibited reduced Ag-presenting efficiency. We conclude that the ability of phagocytosed, particulate Ag to target early phagosomes results in more efficient Ag presentation.
尽管人们公认颗粒性抗原在体内比可溶性抗原更具免疫原性，但尚不清楚这种效应是否仅能通过抗原呈递细胞（APC）摄取的增强来解释。在本研究中，我们证明囊泡大小可调节小鼠巨噬细胞呈递抗原的效率，并且这种效应伴随着抗原运输的深刻变化。大颗粒（560 nm）制备的抗原被递送至早期内体样、未成熟吞噬体，而较小的囊泡（155 nm）和可溶性抗原则迅速定位于晚期内体/溶酶体。然而，在这两个区室中均可检测到肽/Ⅱ类复合物。摄取大囊泡时形成的吞噬体招募抗原加工装置，同时保留早期内体的特征。相反，较小的囊泡绕过该区室，似乎更快地进入溶酶体区室，并表现出降低的抗原呈递效率。我们得出结论，吞噬的颗粒性抗原靶向早期吞噬体的能力导致更有效的抗原呈递。
