Abstract
Human TAPBPR is known to function as a Major Histocompatibility Complex class I (MHC-I) peptide exchange catalyst that shapes the peptide repertoire presented to immune cells. However, investigations characterizing TAPBPR from other species are limited. Here, we characterize mouse TAPBPR, exploring its association partners in mouse cell lines and comparing its function to human TAPBPR. We find that mouse TAPBPR binds MHC-I and calnexin, with a notably sustained interaction with H2-D(b) compared to H2-K(b). We reveal that mouse TAPBPR restricts the peptide repertoire presented on H2-D(b) and H2-K(b) on MC-38 cells. Intriguingly, mouse TAPBPR presence promotes the selection of peptides with a C-terminal methionine on H2-K(b). We reveal that in the presence of high-affinity peptides, mouse TAPBPR can promote loading of both H2-D(b) and H2-K(b). Furthermore, mouse TAPBPR efficiently loaded a peptide with a C-terminal methionine onto H2-K(b). Together, our findings suggest that mouse TAPBPR plays an important role in shaping the MHC-I immunopeptidome by functioning as a peptide editor, similar to its human counterpart.