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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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Antigens, CD / genetics
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Antigens, CD / metabolism
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CD4-Positive T-Lymphocytes / classification
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cytotoxicity Tests, Immunologic* / methods
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Humans
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Immunophenotyping* / methods
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Mitogen / genetics
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Receptors, Mitogen / metabolism
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / chemical synthesis
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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Vaccines, DNA / chemical synthesis
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology
Substances
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Adjuvants, Immunologic
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Antigens, CD
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CLEC12A protein, human
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CLEC12A protein, mouse
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CLEC9a protein, human
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Clec9a protein, mouse
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DEC-205 receptor
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Lectins, C-Type
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Minor Histocompatibility Antigens
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Mitogen
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Recombinant Fusion Proteins
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Vaccines, DNA