Zhou F, Watkins S C, Huang L
Department of Pharmacology, University of Pittsburgh School of Medicine, PA.
Immunobiology. 1994 Feb;190(1-2):35-52. doi: 10.1016/S0171-2985(11)80282-2.
We describe in this report the characterization and kinetics of MHC class I-restricted presentation of a soluble antigen delivered by liposomes. pH-sensitive liposomes delivered ovalbumin (OVA) to the class I pathway more efficiently than pH-insensitive liposomes; the latter showed competence in the class I-restricted sensitization only when a large antigen loading dose was used. Such sensitization of EL4 cells resulted from substantial delivery of the ingested liposomal OVA to the cytosolic compartment as revealed with immunogold electron microscopy. Most of the ingested liposomal OVA were rapidly catabolized and released into the extracellular medium. The residual processed antigen took about 2 h to egress to the cell surface for recognition by CTL. The liposome-mediated antigen presentation exhibited a transient kinetics which was manipulable with antigen dose. Brefeldin A, an ER-to-Golgi transport inhibitor, strongly inhibited such presentation. The antigens displayed on the cell surface could also be removed by a brief acid wash of the cells and subsequently reappeared on the surface if an intracellular pool of antigen existed at the time of acid wash.
我们在本报告中描述了脂质体递送的可溶性抗原的MHC I类限制性呈递的特征和动力学。pH敏感脂质体比pH不敏感脂质体更有效地将卵清蛋白(OVA)递送至I类途径;后者仅在使用大剂量抗原负载时才表现出I类限制性致敏能力。免疫金电子显微镜显示,EL4细胞的这种致敏作用源于摄取的脂质体OVA大量递送至胞质区室。大部分摄取的脂质体OVA迅速被分解代谢并释放到细胞外培养基中。残留的加工抗原需要约2小时才能排出到细胞表面以供CTL识别。脂质体介导的抗原呈递表现出一种短暂的动力学,可通过抗原剂量进行调控。布雷菲德菌素A,一种内质网到高尔基体的转运抑制剂,强烈抑制这种呈递。细胞表面展示的抗原也可以通过对细胞进行短暂酸洗去除,如果酸洗时存在细胞内抗原池,随后抗原会再次出现在表面。