MHC class I molecules function to present peptides comprised of eight to 11
residues to CD8(+) T lymphocytes. Here we review the efforts of our labora
tory to understand how cells generate such peptides from viral gene product
s. We particularly focus on the nature of substrates acted on by cytosolic
proteases, the contribution of proteasomes and non-proteasomal proteases to
peptide generation, the involvement of ubiquitination in peptide generatio
n, the intracellular localization of proteasome generation of antigenic pep
tides, and the trimming of peptides in the endoplasmic reticulum.