Making sense of mass destruction: quantitating MHC class I antigen presentation

MHC class I molecules bind short peptides and present them to CD8+ T cells. Contrary to textbook descriptions, the generation of MHC class-I-associated peptides from endogenous proteins is a highly dynamic and remarkably inefficient process. Here, we describe recent experiments that show how nascent and mature proteins are degraded into peptides that are trimmed, transported and trimmed again to enable presentation of a small portion of the generated peptides. By linking the failure rate of protein synthesis with antigen presentation, a rapid T-cell response is ensured, which is crucial in combating viral infections. Presentation on MHC class I molecules is achieved by less than 0.1% of the specific peptides that have survived intracellular destruction. The other peptides are converted into free amino acids that are used for recycling into new proteins.