Antigen processing and presentation

The notion that major histocompatibility complex (MHC) molecules bind foreign antigens and present them to T lymphocytes is now more than 30 years old. The more advanced concepts that they actually bind small peptides from both self and foreign proteins, that the complex of foreign peptide and MHC molecule is the specific element that is recognized by T cells, and the nature of the binding interaction between peptides and both MHC class I and class II molecules have been understood in principle, if not in detail, for 15 years or so. The precise subject of this volume, antigen processing and presentation, really started in the early 1980s with the work of Emil Unanue and Howard Grey, who showed that protein antigens had to be proteolytically processed after endocytosis by antigenpresenting cells before CD4 T cells could recognize MHC class II-associated peptides derived from them. A few years later, the equivalent observations for MHC class I molecules emerged, chiefly from the work of Alain Townsend, who showed that viral proteins synthesized in the cytosol of an infected cell were the source of the peptides associated with MHC class I molecules that were recognized by CD8 T cells. In the years since then, a large number of investigators have uncovered many of the mechanisms that govern the generation of complexes of peptides with both MHC class I and class II molecules, educating and entertaining the specialists in the field as well as immunologists and cell biologists in general. Antigen processing is an interesting amalgam of cellular housekeeping functions and specialized processes. In the case of MHC class I-restricted antigen processing, proteasomes, which serve a variety of cellular functions (e.g. cytoplasmic protein turnover, regulated degradation of cyclins during the cell cycle, and regulation of nuclear factor-kB Immunological Reviews 2005 Vol. 207: 5–7 Printed in Singapore. All rights reserved