Abstract
Which peptides are selected for presentation by major histocompatibility complex class-I (MHC-I) molecules is a key determinant of successful immune responses. Peptide selection is co-ordinated by the tapasin and TAP Binding PRotein (TAPBPR) proteins, which ensure MHC-I molecules preferentially acquire high-affinity-binding peptides. New structural analyses have offered insight into how tapasin achieves this function within the peptide-loading complex (PLC) (comprising the Transporter associated with Antigen Presentation (TAP) peptide transporter, tapasin-ERp57, MHC-I and calreticulin), and how TAPBPR performs a peptide editing function independently of other molecules. The new structures reveal nuances in how tapasin and TAPBPR interact with MHC-I, and how calreticulin and ERp57 complement tapasin to exploit the plasticity of MHC-I molecules to achieve peptide editing.