title: Angiotensin-converting enzyme affects the presentation of MHC class II antigens.
abstract: Antigen processing and presentation through the MHC class II pathway is critical for activating T helper cells. Angiotensin-converting enzyme (ACE) is a carboxyl peptidase expressed by antigen-presenting cells. By analysis of ACE null (knockout), wild-type, and ACE-overexpressing (ACE10) mice and the antigen-presenting cells derived from these mice, we found that ACE has a physiological role in the processing of peptides for MHC class II presentation. The efficiency of presenting MHC class II epitopes from ovalbumin (OVA) and hen egg lysosome is markedly affected by cellular ACE levels. Mice overexpressing ACE in myeloid cells have a much more vigorous CD4+T-cell and antibody response when immunized with OVA. ACE is present in the endosomal pathway where MHC class II peptide processing and loading occur. The efficiency of MHC class II antigen presentation can be altered by ACE overexpression or ACE pharmacological inhibition. Thus, ACE is a dynamic participant in processing MHC class II peptides. Manipulation of ACE expression by antigen-presenting cells may prove to be a novel strategy to alter the immune response.
authors.affiliation: Laboratory of Molecular Medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.|Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Tuantuan
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.affiliation: Laboratory of Molecular Medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Physiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D010047:Ovalbumin; D007703:Peptidyl-Dipeptidase A