PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

主要组织相容性复合体(MHC)的I类分子 与b微球蛋白(BM)复合的高度多态的重链。 几乎所有类型的细胞都表达I类分子。他们的 唯一的作用是结合抗原，并将它们呈递给T细胞 CD8分子(TCD8+)。TCD8+在根除 细胞内病原体和肿瘤。它们也是一个重要的原因 免疫病理学，参与器官排斥和自身免疫 疾病。 在理解物理性质方面取得了迅速的进展 抗原-I类复合体以及抗原是如何产生的 与细胞中的I类分子联系在一起。现在很明显 来自胞浆蛋白质池的抗原是 通过MHC编码的转运体转移到胞外室 很复杂。一旦从胞浆中转运出来，抗原就会与I类结合。 分子并被输送到细胞表面。 在过去的一年里，我们继续对组件和 MHC I类分子的贩运，并在一些 正面： 1)我们获得了第一个直接证据，证明了多肽与 早期胞腔中的I类分子， 2)我们开发了一种抗原肽的荧光衍生物，并 利用这些探测器做出了几项关于 I类分子和抗原肽的细胞内运输， 3)建立了一种新的I类分子定量分析方法。 表达，并利用这一分析获得了对I类的新见解 贩卖细胞。

Class I molecules of the major histocompatibility complex (MHC) consist of a highly polymorphic heavy chain complexed to b microglobulin (bm). Class I molecules are expressed on virtually all cell types. Their sole function is to bind antigens and present them to T cell bearing CD8 molecules (TCD8+ ). TCD8+ play a critical role in eradicating intracellular pathogens and tumors. They are also a significant cause of immunopathology, being involved in organ rejection and autoimmune diseases. There has been rapid progress in understanding the physical nature of the antigen-class I complex and in how antigens are generated and become associated with class I molecules in cells. It is now apparent that antigens derived from a cytosolic pool of proteins are translocated into an exocytic compartment by a MHC encoded transporter complex. Once transported from the cytosol, antigens bind to class I molecules and are transported to the cell surface. In the past year we have continued our studies on the assembly and trafficking of MHC class I molecules and have made progress on a number of fronts: 1) we obtained the first direct evidence that peptides associate with class I molecules in an early exocytic compartment, 2) we developed fluorescent derivatives of an antigenic peptides and used these probes to make several novel discoveries about the intracellular trafficking of class I molecules and antigenic peptides, 3) we developed a novel quantitative assay for class I molecule expression and used this assay to gain new insights into class I trafficking in cells.