At the crossroads of cell biology and immunology: DRiPs and other sources of peptide ligands for MHC class I molecules

CD8(+) T cells are a critical element of vertebrate immune responses to vir uses and other intracellular parasites. They roam the body, monitoring cell s for the presence of foreign peptides associated with MHC class I molecule s of the major histocompatibility complex (MHC), Although it is clear that most of these peptides are generated through the action of proteasomes, the nature of the substrates degraded by proteasomes is an open question. Rece nt findings indicate that the major pool of substrates consists of a hetero geneous subset of proteins that are degraded within minutes of their synthe sis. Evidence suggests that the fraction of newly synthesized proteins targ eted for destruction is remarkably high - 30% or more, depending on cell ty pe - possibly because they are defective in some way and cannot reach their intended conformation or location cellular in a time frame deemed appropri ate by cells.