How a tailor achieves the perfect fit.

Most antigenic peptides that bind stably to a major histocompatibility complex (MHC) I molecule for display to the immune system are approximately the same length, thanks in part to the expert trimming done by endoplasmic reticulum aminopeptidases (ERAPs), the final peptidases in the antigen-presentation pathway. An open question is whether ERAPs edit peptides to this optimal length while they are bound to MHC I molecules (using the latter as a pattern of sorts) or by free hand. Mavridis et al. present multiple lines of evidence that this trimming cannot readily occur on MHC I molecules, but rather only in solution, suggesting that ERAPs work alone to tailor the perfect fit for the immunopeptidome.