Mouse TAPBPR functions as an MHC-I peptide exchange catalyst

Human TAPBPR is known to function as a Major Histocompatibility Complex class I (MHC-I) peptide exchange catalyst which shapes the peptide repertoire presented to immune cells. Never14theless, 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-Db compared to H2-Kb. We reveal mouse TAPBPR mediates peptide exchange on both H2-Db and H2-Kb, restricting the peptide repertoire presented on MC-38 cells. Intriguingly, mouse TAPBPR promotes the selection of peptides with a C-terminal methionine on H2-Kb. Together, our findings establish that mouse TAPBPR plays an important role in shaping the MHC-I immunopeptidome by functioning as a peptide editor, like its human counterpart.