title: Antigen delivery via two molecules on the CD8- dendritic cell subset induces humoral immunity in the absence of conventional "danger".
abstract: Targeting antigen to dendritic cells (DC) in vivo might be an effective method of modulating immune responses. Given the functional specializations among DC subsets, we investigated how targeting different receptors on different DC subsets may influence antibody (Ab) production. We show here that targeting FIRE (F4/80-like receptor) or CIRE (C-type lectin receptor), two molecules expressed on the surface of immature CD8- DC in the mouse, increases Ab production 100-1000-fold over a non-targeted control. This response was equivalent to that achieved with CpG adjuvant. In contrast, targeting CD205, which is primarily expressed on CD8+ DC, did not elicit an Ab response unless an adjuvant was added. Strong Ab responses in FcRgamma-/- mice, and with the use of F(ab')2 fragments, confirmed that FIRE and CIRE targeting was due to specific rather than FcR or complement binding. Our findings may reflect differences in the ability of CD8+ and CD8- DC subsets to stimulate immune responses in vivo. Although the consensus view is that Ag presentation on DC in their steady state leads to tolerance, the Ab enhancement from FIRE and CIRE targeting in the apparent absence of any "danger" or inflammatory signal would suggest that targeting certain DC molecules can supplant the need for external adjuvants for eliciting immune responses.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Corbett
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.forename: Brent S
authors.initials: BS
authors.lastname: McKenzie
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Brady
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wright
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Mottram
authors.forename: P Mark
authors.initials: PM
authors.lastname: Hogarth
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hodder
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000276:immunology; D005260:Female; D037181:Lectins, C-Type / Q000276:immunology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; C093569:DEC-205 receptor; C464944:Emr4 protein, mouse; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor