Plumbing the sources of endogenous MHC class I peptide ligands

Abstract

From fish to fowl to pharaohs, nearly all cells in jawed vertebrates constitutively process and present peptides derived from endogenously synthesized polypeptides. Such peptides, snug in the binding groove of cell surface MHC class I molecules, enable CD8(+) T cell mediated immunosurveillance of viruses, other intracellular pathogens, and spontaneously arising tumors. The MHC class I system also plays an important role in olfactory-based vertebrate mate selection and perhaps even in preventing direct transmission of tumors between individuals. Recent findings indicate that MHC class I bound peptides are generated at higher efficiency from rapidly degraded polypeptides (including defective ribosomal products) than from old proteins. Intimately linking translation and antigen presentation makes perfect sense for immunosurveillance of acute virus infections, in which speed is of the essence to minimize viral replication, pathogenesis and transmission. The intriguing question of how translation is linked to presentation has prompted the immunoribosome hypothesis of immunosurveillance, which posits that MHC class I peptide ligands are preferentially generated from a subset of translation products.