Pathways of antigen processing and presentation

CD8+ and CD4+ T lymphocytes recognise peptides stably bound to class I or class II MHC molecules, respectively. These complexes are assembled intracellularly during the biosynthesis and trafficking of MHC molecules. It is now clear that a number of different molecules and macromolecular complexes are drafted in to assist this process. Some of these are chaperones which appear to be dedicated to assisting MHC molecules capture peptides, whilst others may have additional cellular functions. Peptides form an integral part of the final MHC glycoprotein structure and their availability can regulate the kinetics and level of expression of MHC molecules on the cell surface. In vivo, significant time may elapse between generation of peptide/MHC complexes and their recognition by T cells. This requires that the complexes generated are stable and long-lived on the cell surface. Several mechanisms appear to contribute to the generation and display of long-lived complexes. Some pathogens have evolved mechanisms to evade and interfere with presentation of their own antigens. The strategies used are many and varied and are particularly well exemplified by the interaction of viral gene products with the MHC class I assembly pathway. Here, we provide an overview of what is currently known about the cellular biochemistry of antigen processing and the assembly of class I and class II MHC molecules.