Delivery of protein antigen to the major histocompatibility complex class I-restricted antigen presentation pathway.
Delivery of protein antigen to the major histocompatibility complex class I-restricted antigen presentation pathway.
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DOI：
10.3109/10611869509059210
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发表时间：
1995
影响因子：
4.5
通讯作者：
F. Zhou;L. Huang
中科院分区：
文献类型：
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作者：
F. Zhou;L. Huang
主要组织相容性复合体（MHC）I类限制性抗原呈递通常需要在抗原呈递细胞（APC）的胞质溶胶中合成蛋白质抗原。如果将外源蛋白质抗原引入APC的胞质区室，则该蛋白质抗原可以进入I类呈递途径。从内吞囊泡释放蛋白抗原的方法已被用于递送蛋白抗原以供I类限制性细胞毒性T淋巴细胞（CTL）识别。这些包括渗透压休克、电穿孔、阳离子和pH敏感性脂质体。另一种方法是递送编码蛋白抗原的基因。在这种情况下，APC用在胞质溶胶中合成“外源蛋白”的基因转染。靶向用于体内CTL诱导的蛋白抗原的递送遵循不同的策略，并且通常需要细胞内/膜性质的抗原载体，例如脂质体、免疫刺激复合物和/或脂质缀合物。负责清除抗原的巨噬细胞在CTL诱导中起重要作用。最佳的CTL诱导疫苗除了其将抗原递送至I类途径的活性之外还必须含有其它免疫调节活性。通过递送包埋在脂质体中的外源性抗原来减弱病毒感染和提高抗肿瘤免疫的尝试已经成功。这些动物模型研究在潜在疫苗制剂的开发中具有重要价值。
Major histocompatibility complex (MHC) class I-restricted antigen presentation normally requires a protein antigen to be synthesized in the cytosol of the antigen presenting cell (APC). Exogenous protein antigen could gain access to the class I presentation pathway if the protein is introduced into the cytosolic compartment of the APC. Approaches which release the protein antigen from endocytic vesicles have been employed to deliver protein antigen for the recognition by class I-restricted cytotoxic T lymphocytes (CTL). These include osmotic shock, electroporation, cationic and pH-sensitive liposomes. An alternative approach is to deliver a gene that encodes the protein antigen. In this case, the APC is transfected with a gene which synthesizes the "exogenous protein" in the cytosol. Delivery of protein antigen targeted for CTL induction in vivo follows a different strategy and generally requires an antigen carrier of lipidic/membranous nature, such as liposomes, immunostimulating complexes, and/or lipid conjugates. Macrophages that are responsible for scavenging the antigen play an important role in CTL induction. An optimal CTL inductive vaccine must contain other immuno-modulatory activities in addition to its activity in delivering antigen to the class I pathway. Attempts to attenuate viral infection and to improve anti-tumor immunity have been successful by delivering the exogenous antigen entrapped in liposomes. These animal model studies should be of great value in the development of potential vaccine formulation.