PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

主要组织相容性复合体（MHC）的I类分子 由与B2-微球蛋白复合的高度多态性重链组成。 I类分子在几乎所有细胞类型上表达。他们唯一 其功能是结合抗原并将其呈递给携带CDS的T细胞， 分子。这些T细胞被称为细胞毒性T淋巴细胞（CTLS），这是由于 它们以抗原特异性方式裂解组织相容性细胞的能力。 CTL在根除细胞内病原体中起关键作用， 肿瘤的在消极的一面，它们参与器官排斥， 许多自身免疫性恶液质 在理解宇宙的物理性质方面已经取得了迅速的进展， 抗原-I类复合物以及抗原如何与I类 细胞中的分子。部分基于该实验室的结果， 现在很明显，存在于胞质溶胶中的抗原被转运到 胞吐区室，在那里它们结合I类分子，I类分子将它们携带到 用于CTL识别的细胞表面。 在过去的一年里，我们继续研究抗原处理， 可以定义为蛋白质的结构修饰和运输 能够使决定簇被CTL识别的抗原（通常被埋在 天然蛋白质）与适当亚细胞中的MHC分子相互作用 车厢我们集中讨论了以下问题。其中， 与I类分子发生缔合的隔室？有 用于将蛋白质靶向到胞质抗原处理中的信号 pathway？是否有细胞蛋白的功能，以促进 I类分子与抗原的结合？细胞外蛋白质 靶向细胞溶质抗原加工途径？

Class I molecules of the major histocompatibility complex class (MHC) consist of a highly polymorphic heavy chain complexed to B2-microglobulin. Class I molecules are expressed on virtually all cell types. Their sole function is to bind antigens and present them to T cells bearing, CDS molecules. These T cells are known as cytotoxic T lymphocytes (CTLS) due to their ability to lyse histocompatible cells in an antigen specific manner. CTLs play a critical role in eradicating intracellular pathogens and tumors. On the negative side, they are involved in organ rejection, and in many autoimmune dyscrasias. There has been rapid progress in understanding the physical nature of the antigen-class I complex and in how antigens become associated with class I molecules in cells. Based in part on results from this laboratory, it is now apparent that antigens present in the cytosol are tranlocated into the exocytic compartment where they bind class I molecules which carry them to the cell surface for CTL recognition. In the past year we have continued our studies on antigen processing, which can be defined as the structural modification and trafficking of protein antigens that enable the determinants recognized by CTLs (often buried in native proteins) to interact with MHC molecules in the proper subcellular compartment. We have focused on the following questions. In which exocytic compartment does association with class I molecules occur? Are there signals for targeting proteins into the cytosolic antigen processing pathway? Are there cellular proteins which function to facilitate the association of class I molecules with antigen? Can extracellular proteins be targeted to the cytosolic antigen processing pathway?