Abstract
Injection of antigens coupled to antibodies against the dendritic cell (DC) surface molecule Clec9A has been shown to produce strongly enhanced antibody responses even without co-administration of adjuvants, via antigen presentation by DC on MHC class II and consequent production of follicular helper T cells. A series of mutant mice were tested to determine the DC subtypes responsible for this MHC II presentation of targeted antigen, compared to presentation of antigen on MHC I. A new clec9A null mouse was developed; these mice did not give enhanced antibody production, confirming the response was dependent on Clec9A-expressing DC. However targeting of antigen to Clec9A in batf3 null mice produced enhanced antibody responses despite the marked reduction in CD8(+) DC, the major Clec9A-expressing DC subtype. This was shown to be dependent on efficient MHC II presentation by minor Clec9A-expressing DC subtypes in the environment of the Batf3(-/-) mice, namely early cells of the CD8 DC lineage and the plasmacytoid-related CD8(+) DC subset, but not by plasmacytoid cells themselves. However in normal mice most MHC II presentation of the Clec9A-targeted antigen was by the major CD8(+) DC population, the DC also responsible for presentation on MHC I.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation / immunology*
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Antigen Presentation / immunology
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / immunology*
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CD8 Antigens / immunology
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Cells, Cultured
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Female
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class II / immunology
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / immunology
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology*
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Lymphocyte Activation / immunology
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Male
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Ovalbumin / genetics
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Ovalbumin / immunology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology*
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Repressor Proteins / genetics
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Repressor Proteins / immunology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
Substances
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Basic-Leucine Zipper Transcription Factors
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CD8 Antigens
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Clec9a protein, mouse
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Interferon Regulatory Factors
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Lectins, C-Type
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Receptors, Immunologic
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Repressor Proteins
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SNFT protein, mouse
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interferon regulatory factor-8
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Ovalbumin