PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

主要组织相容性复合体类(MHC)的I类分子 由与B2-微球蛋白络合的高度多态的重链组成。 几乎所有类型的细胞都表达I类分子。他们的鞋底 功能是结合抗原并将它们呈递给携带CDS的T细胞 分子。这些T细胞被称为细胞毒性T淋巴细胞(CTL)，原因是 它们以抗原特异的方式溶解组织相容细胞的能力。 CTL在根除细胞内病原体和 肿瘤。从负面来看，它们与器官排斥反应有关，而且在 许多自身免疫性阅读障碍。 在理解物理性质方面取得了迅速的进展 抗原-I类复合体以及抗原如何与I类相关 细胞中的分子。部分基于这个实验室的结果，它是 现在很明显，存在于细胞质中的抗原被转移到 胞外隔间，它们与携带它们的I类分子结合 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，这是 可以被定义为蛋白质的结构修饰和运输 使CTL识别的决定簇成为可能的抗原(通常埋在 天然蛋白质)与适当亚细胞中的MHC分子相互作用 车厢。我们重点解决了以下几个问题。其中胞外 是否存在与I类分子相关的隔室？在那里吗 靶向蛋白质进入胞浆抗原处理的信号 小路？有没有细胞蛋白起到促进 I类分子与抗原的关联性？胞外蛋白可以 以胞浆抗原处理途径为靶点？

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?