PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

点击翻译按钮获取中文摘要

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.