title: The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement.
abstract: A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the CD8(+) conventional DC and plasmacytoid DC subtypes. A subset of human blood DCs also expressed CLEC9A. A single injection of mice with a mAb against Clec9A, which targets antigens (Ags) to the DCs, produced a striking enhancement of antibody responses in the absence of added adjuvants or danger signals, even in mice lacking Toll-like receptor signaling pathways. Such targeting also enhanced CD4 and CD8 T-cell responses. Thus, Clec9A serves as a new marker to distinguish subtypes of both mouse and human DCs. Furthermore, targeting Ags to DCs with antibodies to Clec9A is a promising strategy to enhance the efficiency of vaccines, even in the absence of adjuvants.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.forename: Anna I
authors.initials: AI
authors.lastname: Proietto
authors.forename: Fatma
authors.initials: F
authors.lastname: Ahmet
authors.forename: Susie
authors.initials: S
authors.lastname: Kitsoulis
authors.forename: Joo
authors.initials: J
authors.lastname: Shin Teh
authors.forename: Jennifer C Y
authors.initials: JC
authors.lastname: Lo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rizzitelli
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Vremec
authors.forename: Serani L H
authors.initials: SL
authors.lastname: van Dommelen
authors.forename: Ian K
authors.initials: IK
authors.lastname: Campbell
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Hal
authors.initials: H
authors.lastname: Braley
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Davey
authors.forename: Patricia
authors.initials: P
authors.lastname: Mottram
authors.forename: Nicholas
authors.initials: N
authors.lastname: van de Velde
authors.forename: Kent
authors.initials: K
authors.lastname: Jensen
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wright
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014612:Vaccines / Q000737:chemistry / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D014612:Vaccines