Ever since A. Townsend, A. McMichael, and coworkers reported 26 years ago that T lymphocytes
recognize short peptide fragments in association with major histocompatibility
complex (MHC) encoded proteins (1), immunologists have been keen to understand how
these fragments are produced, how they are transported to MHC molecules and how they
assemble with them. It was not surprising that the new fi eld of antigen processing attracted
considerable interest, given that peptide presentation by MHC molecules is the key element
in immunological self-non self discrimination, pathogen-speci fi c immune responses,
autoimmunity, and vaccine development. As a result, many aspects of cellular antigen processing
are now understood in great detail, although some other issues (e.g., the nature of
endogenous proteins giving rise to MHC class I ligands, or the cell biology of cross-presentation)
remain to be clari fi ed.