Fig. S3.

Models for the interaction of TAPBPR with MHC-I molecules during peptide loading. Pathways for assembly of MHC-I heavy chain with β₂m, TAPBPR, and either high-affinity (P_HA) or low-affinity (P_LA) peptides are illustrated. MHC-I conformations: MHC-I_NC (nascent chain), MHC-I_PR (peptide-receptive), MHC-I_F (folded) are indicated schematically and are labeled. The nascent MHC-I heavy chain (MHC-I_NC) first folds partially and interacts with β₂m, early in the biosynthetic pathway (1). This peptide-receptive MHC/β₂m complex, MHC-I_PR/β₂m (2) assembles with TAPBPR (3) to form the stabilized TAPBPR/MHC-I_PR/β₂m (4). Encounter complexes, formed with either a high-affinity peptide TAPBPR/MHC-I_PR/P_HA (5) or with a low-affinity peptide TAPBPR/MHC-I_PR/P_LA (7), then serve as precursors either to the fully folded (and stable) MHC-I_F/P_HA complex (6), which can be transported to the cell surface, or to a TAPBPR-free MHC-I_PR/P_LA complex (8), which is unstable but can be stabilized by TAPBPR. The biologically important editing role of TAPBPR is evident in the transition from conformation 7 to conformation 5, which occurs with the exchange of low- for high-affinity peptides.