title: Targeting of the hNC16A collagen domain to dendritic cells induces tolerance to human type XVII collagen.
abstract: Antibodies, specific to murine DEC205, can be used to target antigens to dendritic cells. The immunodominant domain of human type XVII collagen, hNC16A, was fused to this antibody (DEC-hNC16A) and was administered as expression plasmid by gene gun transfection with the aim of inducing tolerance to human type XVII collagen in a skin transplantation model. Mice transfected with DEC-hNC16A were challenged with skin grafts from transgenic mice engineered to express human type XVII collagen. Graft survival was either prolonged or grafts were accepted infinitely (33% and 16%, respectively) upon treatment with DEC-hNC16A while 100% of grafts were rejected in untreated controls. Graft acceptance was associated with the absence of a CD4+ infiltrate and a dense CD8+ T-cell infiltrate and was not strictly dependent on antibody production. Our results show that DEC-hNC16A targets dendritic cells in vivo leading to prolonged survival of transgenic skin grafts. This indicates that DEC205-targeting may be used for the induction of tolerance to skin antigens, which would increase the chances of successful skin gene therapy of epidermolysis bullosa patients.
authors.forename: Monika
authors.initials: M
authors.lastname: Ettinger
authors.forename: Iris K
authors.initials: IK
authors.lastname: Gratz
authors.forename: Christina
authors.initials: C
authors.lastname: Gruber
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.forename: Theron S
authors.initials: TS
authors.lastname: Johnson
authors.forename: Karsten
authors.initials: K
authors.lastname: Mahnke
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Helmut
authors.initials: H
authors.lastname: Hintner
authors.forename: Doris
authors.initials: D
authors.lastname: Peckl-Schmid
authors.forename: Johann W
authors.initials: JW
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015316:Genetic Therapy; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D024041:Non-Fibrillar Collagens / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology*; D014162:Transfection; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII