title: Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype.
abstract: Three surface molecules of mouse CD8(+) dendritic cells (DCs), also found on the equivalent human DC subpopulation, were compared as targets for Ab-mediated delivery of Ags, a developing strategy for vaccination. For the production of cytotoxic T cells, DEC-205 and Clec9A, but not Clec12A, were effective targets, although only in the presence of adjuvants. For Ab production, however, Clec9A excelled as a target, even in the absence of adjuvant. Potent humoral immunity was a result of the highly specific expression of Clec9A on DCs, which allowed longer residence of targeting Abs in the bloodstream, prolonged DC Ag presentation, and extended CD4 T cell proliferation, all of which drove highly efficient development of follicular helper T cells. Because Clec9A shows a similar expression pattern on human DCs, it has particular promise as a target for vaccines of human application.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.forename: Fatma
authors.initials: F
authors.lastname: Ahmet
authors.forename: Susie
authors.initials: S
authors.lastname: Kitsoulis
authors.forename: Soo San
authors.initials: SS
authors.lastname: Wan
authors.forename: David
authors.initials: D
authors.lastname: Vremec
authors.forename: Chin-Nien
authors.initials: CN
authors.lastname: Lee
authors.forename: Belinda
authors.initials: B
authors.lastname: Phipson
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.forename: Yu
authors.initials: Y
authors.lastname: Kato
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Davey
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; C485220:CLEC12A protein, human; C529398:CLEC12A protein, mouse; C530206:CLEC9a protein, human; C529914:Clec9a protein, mouse; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA