Expression of angiotensin-converting enzyme changes major histocompatibility complex class I peptide presentation by modifying C termini of peptide precursors.
We recently reported a mouse model called ACE 10/10 in which macrophages overexpress the carboxypeptidase angiotensin-converting enzyme (ACE). These mice have an enhanced inflammatory response to tumors that markedly inhibits tumor growth. Here, we show that ACE modifies the C termini of peptides for presentation by major histocompatibility complex (MHC) class I molecules. The peptide-processing activity of ACE applies to antigens from either the extracellular environment (cross-presentation) or antigens produced endogenously. Consistent with its role in MHC class I antigen processing, ACE localizes to the endoplasmic reticulum. ACE overexpression does not appear to change the overall supply of peptides available to MHC class I molecules. The immunization of wild type mice previously given ACE 10/10 macrophages enhances the efficiency of antigen-specific CD8+ T cell priming. These data reveal that ACE is a dynamic participant in fashioning the peptide repertoire for MHC class I molecules by modifying the C termini of peptide precursors. Manipulation of peptidase expression by antigen-presenting cells may ultimately prove a useful strategy to enhance the immune response.
Shen
Xiao Z
XZ
Department of Pathology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Lukacher
Aron E
AE
Billet
Sandrine
S
Williams
Ifor R
IR
Bernstein
Kenneth E
KE
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000201:enzymology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D007703:Peptidyl-Dipeptidase A