title: The carboxypeptidase ACE shapes the MHC class I peptide repertoire.
abstract: The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8(+) T cell-mediated adaptive immune responses. Aminopeptidases have been linked to the editing of peptides for MHC class I loading, but carboxy-terminal editing is thought to be due to proteasome cleavage. By analysis of wild-type mice and mice genetically deficient in or overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now identified ACE as having a physiological role in the processing of peptides for MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I peptides. The lack of ACE exposed new antigens but also abrogated some self antigens. ACE had substantial effects on the surface expression of MHC class I in a haplotype-dependent manner. We propose a revised model of peptide processing for MHC class I by introducing carboxypeptidase activity into the process.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Billet
authors.forename: Chentao
authors.initials: C
authors.lastname: Lin
authors.forename: Derick
authors.initials: D
authors.lastname: Okwan-Duodu
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A; D046988:Proteasome Endopeptidase Complex