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We describe the cloning and characterization of Siglec-H, a novel murine CD33-related siglec-like molecule with 2 immunoglobulin domains. Unlike other CD33-related siglecs, Siglec-H lacks tyrosine-based signaling motifs in its cytoplasmic tail. Although Siglec-H has the typical structural features required for sialic acid binding, no evidence for carbohydrate recognition was obtained. Specific monoclonal and polyclonal antibodies (Abs) were raised to Siglec-H and used to define its cellular expression pattern and functional properties. By flow cytometry, Siglec-H was expressed specifically on plasmacytoid dendritic cell (pDC) precursors in bone marrow, spleen, blood, and lymph nodes. Staining of tissue sections showed that Siglec-H was also expressed in a subset of marginal zone macrophages in the spleen and in medullary macrophages in lymph nodes. Using bone marrow-derived pDC precursors that express Siglec-H, addition of Abs did not influence cytokine production, either in the presence or absence of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG). In comparison, Siglec-H functioned as an endocytic receptor and mediated efficient internalization of anti-Siglec-H Abs. By immunizing mice with ovalbumin-conjugated anti-Siglec-H Ab in the presence of CpG, we demonstrate generation of antigen-specific CD8 T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.

Original publication

DOI

10.1182/blood-2005-09-3842

Type

Journal article

Journal

Blood

Publication Date

01/05/2006

Volume

107

Pages

3600 - 3608

Keywords

Amino Acid Sequence, Animals, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Base Sequence, CD8-Positive T-Lymphocytes, Cloning, Molecular, DNA, Complementary, Dendritic Cells, Endocytosis, Gene Expression, Hematopoietic Stem Cells, Mice, Mice, Inbred Strains, Mice, Knockout, Molecular Sequence Data, N-Acetylneuraminic Acid, Plasma Cells, Receptors, Immunologic, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Sialic Acid Binding Ig-like Lectin 3