Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors

被引:194
|
作者
Zhang, JQ
Raper, A
Sugita, N
Hingorani, R
Salio, M
Palmowski, MJ
Cerundolo, V
Crocker, PR [1 ]
机构
[1] Univ Dundee, Div Cell Biol & Immunol, Wellcome Trust Bioctr Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland
[2] Niigata Univ, Grad Sch Med & Dent Sci, Dept Oral Biol Sci, Div Periodontol, Niigata, Japan
[3] BD Biosci, San Diego, CA USA
[4] Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX1 2JD, England
基金
英国惠康基金;
关键词
D O I
10.1182/blood-2005-09-3842
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 CD8T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.
引用
收藏
页码:3600 / 3608
页数:9
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