title: Targeting antigen to MHC class II molecules promotes efficient cross-presentation and enhances immunotherapy.
abstract: An efficient pathway of cross-presentation common to a range of dendritic cell (DC) populations was identified by targeting Ag to MHC class II molecules. This finding was achieved by conjugating Ag to M1, which is a modified version of the superantigen streptococcal mitogenic exotoxin Z-2 that binds to MHC class II molecules but cannot directly stimulate T cells. M1 conjugates were efficiently presented to CD4(+) and CD8(+) T cells by bone marrow-derived DC and Langerhans cells in vitro. Whereas nonconjugated Ag was preferentially cross-presented by splenic CD8alpha(+) DC in vivo, M1-conjugated Ag was cross-presented by all dendritic subtypes assessed. Potent effector T cell responses with antitumor activity were elicited when M1 conjugates were injected together with an adjuvant. This method of Ag delivery has significant potential in therapeutic applications.
authors.affiliation: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors.forename: Nina
authors.initials: N
authors.lastname: Dickgreber
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Kylie M
authors.initials: KM
authors.lastname: Price
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Farrand
authors.forename: Kristy
authors.initials: K
authors.lastname: Manning
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Angel
authors.forename: P Rod
authors.initials: PR
authors.lastname: Dunbar
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
authors.forename: John D
authors.initials: JD
authors.lastname: Fraser
authors.forename: B Thomas
authors.initials: BT
authors.lastname: Bäckström
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005098:Exotoxins / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D019496:Cancer Vaccines; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D018089:Superantigens; C107894:mitogenic exotoxin Z protein, Streptococcus