ERAAP shapes the peptidome associated with classical and non-classical MHC class I molecules

摘要

The peptide repertoire presented by classical as well as non-classical MHC I molecules is altered in the absence of the ER aminopeptidase associated with antigen processing (ERAAP). To characterize the extent of these changes, peptides from cells lacking ERAAP were eluted from the cell surface and analyzed by high-throughput mass spectrometry. We found that the majority of peptides found in WT cells were retained in the absence of ERAAP. In contrast, a subset of “ERAAP-edited” peptides was lost in WT cells, and ERAAP-deficient cells presented an unique “unedited” repertoire. A substantial fraction of MHC-associated peptides from ERAAP-deficient cells contained N-terminal extensions and had a different molecular composition than those from WT cells. We found that the number and immunogenicity of peptides associated with non-classical MHC I was increased in the absence of ERAAP. Conversely, only peptides presented by classical MHC I were immunogenic in ERAAP-sufficient cells. Finally, MHC I peptides were also derived from different intracellular sources in ERAAP-deficient cells.