Figure 9. Model of the relationship between tapasin and TAPBPR in shaping the peptide repertoire expressed on MHC class I.
(A) Upstream of the PLC, in an environment in which peptides suitable for MHC class I binding are likely to be at a low concentration, TAPBPR might help stabilise a peptide-receptive conformation of MHC class I, but would not directly assist in peptide loading, peptide exchange or directly increase the abundance of peptide:MHC complexes due to a shortage of peptide. (B) The optimal peptide loading environment for MHC class I is presumably within the PLC where the concentration of peptides suitable for MHC class I is the highest and where MHC I are held in a peptide-receptive conformation by tapasin. (C) Once peptide:MHC I complexes are released from the PLC, TAPBPR-mediated dissociation would attempt to remove peptide from MHC class I. If a high affinity peptide was bound to the MHC I molecules, TAPBPR would not be able to remove it. If TAPBPR can cause the dissociation of peptide, peptide exchange could ensue if suitable replacement peptides were available. However, the further away from the PLC and/or the further down the MHC class I peptide gradient TAPBPR works there may be a shortage of suitable replacement peptides. In this situation TAPBPR is unlikely to load the peptide-receptive MHC class I and may assist in the recycling of MHC I molecules. By functioning as a peptide exchange catalyst in a relatively peptide deficient environment, TAPBPR could increase the affinity of the peptide:MHC I complexes or restrict the diversity of peptide:MHC I complexes which are presented to the cell surface.