Rao M, Alving C R
Department of Membrane Biochemistry, Bldg. 40, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Adv Drug Deliv Rev. 2000 Mar 30;41(2):171-88. doi: 10.1016/s0169-409x(99)00064-2.
Liposomes have the well-known ability to channel protein and peptide antigens into the MHC class II pathway of phagocytic antigen-presenting cells (APCs) and thereby enhance the induction of antibodies and antigen-specific T cell proliferative responses. Liposomes also serve as an efficient delivery system for entry of exogenous protein and peptide antigens into the MHC class I pathway and thus are very efficient inducers of cytotoxic T cell responses. Soluble antigens that are rendered particulate by encapsulation in liposomes are localized both in vacuoles and in the cytoplasm of bone marrow-derived macrophages. Utilizing fluorophore-labeled proteins encapsulated in liposomes we have addressed the question of how liposomal antigens enter the MHC class I pathway. After phagocytosis of the liposomes, the fluorescent liposomal protein and liposomal lipids enter the cytoplasm where they are processed by the proteasome complex. The processed liposomal protein is then transported via the TAP complex into the endoplasmic reticulum and the Golgi complex. Both the liposomal lipids and the liposomal proteins appear to follow the same intracellular route and they are processed as a protein-lipid unit. In the absence of a protein antigen (empty liposomes), there is no organelle-specific localization of the liposomal lipids. In contrast, when a protein is encapsulated in these liposomes, the distribution of the liposomal lipids is dramatically affected and the liposomal lipids localize to the trans-Golgi area. Localization of the protein in the trans-Golgi area requires liposomal lipids. Similarly, for the localization of liposomal lipids in the trans-Golgi area, there is an obligatory requirement for protein. Therefore, the intracellular trafficking patterns of liposomal lipids and liposomal protein are reciprocally regulated. Presence of both liposomal lipids and liposomal protein in the trans-Golgi therefore facilitates the entry of liposomal antigens into the MHC class I pathway. It is also possible that liposomal lipids are presented to T cells via the recently described CD1 pathway for lipid antigens. Because liposome-formulated vaccines have the potential to stimulate antibody as well as cellular immune responses to protein and lipid components, this approach could prove to be extremely useful in designing vaccine strategies.
脂质体具有将蛋白质和肽抗原导入吞噬性抗原呈递细胞（APC）的MHC II类途径的能力，从而增强抗体诱导和抗原特异性T细胞增殖反应。脂质体还可作为一种有效的递送系统，使外源性蛋白质和肽抗原进入MHC I类途径，因此是细胞毒性T细胞反应的高效诱导剂。通过包裹在脂质体中而变成颗粒状的可溶性抗原，既存在于骨髓来源巨噬细胞的液泡中，也存在于其细胞质中。利用包裹在脂质体中的荧光团标记蛋白，我们研究了脂质体抗原如何进入MHC I类途径这一问题。脂质体被吞噬后，荧光脂质体蛋白和脂质体脂质进入细胞质，在那里它们被蛋白酶体复合物加工处理。然后，经过加工的脂质体蛋白通过TAP复合物转运到内质网和高尔基体。脂质体脂质和脂质体蛋白似乎遵循相同的细胞内途径，并且它们作为蛋白质-脂质单元被加工处理。在没有蛋白质抗原（空脂质体）的情况下，脂质体脂质没有细胞器特异性定位。相反，当蛋白质被包裹在这些脂质体中时，脂质体脂质的分布会受到显著影响，脂质体脂质会定位于反式高尔基体区域。蛋白质在反式高尔基体区域的定位需要脂质体脂质。同样，对于脂质体脂质在反式高尔基体区域的定位，蛋白质也是必不可少的。因此，脂质体脂质和脂质体蛋白的细胞内运输模式相互调节。反式高尔基体中脂质体脂质和脂质体蛋白的同时存在，因此促进了脂质体抗原进入MHC I类途径。脂质体脂质也有可能通过最近描述的脂质抗原CD1途径呈递给T细胞。由于脂质体制剂疫苗有可能刺激针对蛋白质和脂质成分的抗体以及细胞免疫反应，这种方法在设计疫苗策略方面可能会被证明极其有用。
