Nuchtern J G, Biddison W E, Klausner R D
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Nature. 1990 Jan 4;343(6253):74-6. doi: 10.1038/343074a0.
Models for antigen presentation have divided the world of antigens into two categories, endogenous and exogenous, presented to T cells by class I and class II major histocompatibility complex (MHC) encoded molecules, respectively. Exogenous antigens are though to be taken up into peripheral endosomal compartments where they are processed for binding to class II MHC molecules. Endogenous antigens are either synthesized or efficiently delivered to the cytoplasm before being partially degraded in an as yet undefined way, and complexed with class I MHC molecules. A useful phenotypic distinction between the two pathways has been the sensitivity to weak bases, such as chloroquine, which is a property only of the exogenous pathway. The fungal antibiotic brefeldin A (BFA), which blocks protein transport from the endoplasmic reticulum to the Golgi network, also blocks class I-restricted antigen-presentation, providing us with the corresponding marker of the endogenous pathway. Experiments with influenza virus antigens have supported the view that class II MHC molecules can present exogenous but not endogenous antigen, whereas the observation that class II MHC molecules present measles virus non-membrane antigens by a chloroquine-insensitive pathway suggests that this is not always the case. We show here that influenza A matrix protein can be effectively presented to class II-restricted T cells by two pathways: one of which is chloroquine-sensitive, BFA-insensitive, the other being chloroquine-insensitive and BFA-sensitive. Our results indicate that both class I and class II molecules can complex with antigenic peptides in a pre-Golgi compartment and favour a unified mechanism for MHC-restricted endogenous antigen presentation.
抗原呈递模型将抗原世界分为内源性和外源性两类，分别由I类和II类主要组织相容性复合体（MHC）编码的分子呈递给T细胞。外源性抗原被认为被摄取到外周内体区室，在那里它们被加工以结合II类MHC分子。内源性抗原要么在以一种尚未明确的方式被部分降解之前被合成或有效地递送到细胞质中，并与I类MHC分子形成复合物。这两条途径之间一个有用的表型区别是对弱碱（如氯喹）的敏感性，这是外源性途径独有的特性。真菌抗生素布雷菲德菌素A（BFA）可阻断蛋白质从内质网到高尔基体网络的转运，也可阻断I类限制性抗原呈递，为我们提供了内源性途径的相应标志物。用流感病毒抗原进行的实验支持了这样的观点，即II类MHC分子可以呈递外源性但不能呈递内源性抗原，而II类MHC分子通过对氯喹不敏感的途径呈递麻疹病毒非膜抗原的观察结果表明情况并非总是如此。我们在此表明，甲型流感病毒基质蛋白可通过两条途径有效地呈递给II类限制性T细胞：一条途径对氯喹敏感、对BFA不敏感，另一条途径对氯喹不敏感且对BFA敏感。我们的结果表明，I类和II类分子都可以在高尔基体前区室中与抗原肽形成复合物，并支持MHC限制性内源性抗原呈递的统一机制。
