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

Abstract

CD8+ T cells are a critical element of vertebrate immune responses to viruses and other intracellular parasites. They roam the body, monitoring cells for the presence of foreign peptides associated with MHC class I molecules 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. Recent findings indicate that the major pool of substrates consists of a heterogeneous subset of proteins that are degraded within minutes of their synthesis. Evidence suggests that the fraction of newly synthesized proteins targeted for destruction is remarkably high - 30% or more, depending on cell type - possibly because they are defective in some way and cannot reach their intended conformation or location cellular in a time frame deemed appropriate by cells.