title: Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells.
abstract: Cell-penetrating peptides (CPP) or membrane-translocating peptides such as penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen-presenting cells. Mice immunized with CPP containing immunogens elicit antigen-specific Tc and/or Th responses and could be protected from tumor challenges. In the present paper, we investigate the mechanism of class I and class II antigen presentation of ovalbumin covalently linked to penetratin (AntpOVA) by bone marrow-derived dendritic cells with the use of biochemical inhibitors of various pathways of antigen processing and presentation. Results from our study suggested that uptake of AntpOVA is via a combination of energy-independent (membrane fusion) and energy-dependent pathways (endocytosis). Once internalized by either mechanism, multiple tap-dependent or independent antigen presentation pathways are accessed while not completely dependent on proteasomal processing but involving proteolytic trimming in the ER and Golgi compartments. Our study provides an understanding on the mechanism of antigen presentation mediated by CPP and leads to greater insights into future development of vaccine formulations.
authors.affiliation: School of Medical Sciences, RMIT University, Plenty Road, Bundoora, VIC, 3083, Australia.
authors.forename: Dodie
authors.initials: D
authors.lastname: Pouniotis
authors.affiliation: Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.|DUKE-NUS, 8 College Road, Singapore, 169857, Singapore.
authors.forename: Choon-Kit
authors.initials: CK
authors.lastname: Tang
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.affiliation: Bio-Organic and Medicinal Chemistry Laboratory, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia. gpietersz@burnet.edu.au.|Department of Pathology, University of Melbourne, Parkville, VIC, Australia. gpietersz@burnet.edu.au.|Department of Immunology, Monash University, Melbourne, VIC, Australia. gpietersz@burnet.edu.au.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pietersz
mesh_terms: D000818:Animals; D051943:Antennapedia Homeodomain Protein / Q000276:immunology*; D017951:Antigen Presentation; D001181:Arthropods / Q000276:immunology; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000276:immunology*; D057846:Cell-Penetrating Peptides; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000138:chemical synthesis / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D051943:Antennapedia Homeodomain Protein; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014612:Vaccines; D010047:Ovalbumin; C414409:penetratin
keywords: Antennapedia; Antp; CPP; Cell-penetrating peptides; Cytotoxic T cell epitope; Membrane-translocating peptide; Ovalbumin; TAT; Vaccine