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Published on: April 18, 2016
Dendritic cell-associated lectin-1: a novel dendritic cell-associated, C-type lectin-like molecule enhances T cell
Elizabeth J Ryan1, Aaron J Marshall, Dario Magaletti
1Regional Primate Research Center, Box 357330, University of Washington, Seattle, WA 98195, USA. ejryan@u.washington.edu
Insights
Dendritic cell (DC)-associated lectin-1 (DCAL-1) is a novel C-type lectin expressed on DCs and B cells. DCAL-1 acts as a costimulatory molecule, enhancing CD4+ T cell proliferation and promoting a Th2 response by increasing IL-4 secretion.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Dendritic cell (DC)-associated lectin-1 (DCAL-1) is a novel type II transmembrane C-type lectin-like protein.
- DCAL-1 exhibits restricted expression in hemopoietic cells, primarily DCs and B cells, but not T cells or monocytes.
- The DCAL-1 gene is located on human chromosome 12p12-13 within a cluster of C-type lectin-like loci.
Purpose of the Study:
- To characterize the novel DCAL-1 protein, its expression patterns, and its functional role in immune responses.
- To investigate the potential of DCAL-1 as a costimulatory molecule for T cells.
- To determine the effect of DCAL-1 on T cell proliferation and cytokine secretion.
Main Methods:
- RACE-PCR was used to confirm the consensus sequence of the DCAL-1 gene.
- Sequence alignment was performed to predict splice variants of DCAL-1.
- Fusion proteins of DCAL-1 and CD209 were used to assess T cell responses.
- Monocyte differentiation to CD1a(+) DCs was induced to study DCAL-1 expression.
Main Results:
- DCAL-1 has two predicted splice variants and lacks three cysteine residues crucial for standard carbohydrate recognition domains.
- DCAL-1 mRNA and protein expression increase during monocyte differentiation to DCs and are high on B cells.
- Soluble DCAL-1 enhanced CD4+ T cell proliferation and IL-4 secretion upon CD3 ligation, while CD209 had no effect.
- A population of CD4+ CD45RA+ T cells expressing DCAL-1 ligand was identified.
Conclusions:
- DCAL-1 functions as a T cell costimulatory molecule on DCs and B cells.
- DCAL-1 skews CD4+ T cell responses toward a Th2 phenotype by enhancing IL-4 secretion.
- DCAL-1 represents a novel target for modulating T cell-mediated immunity.
Abstract:
We have characterized dendritic cell (DC)-associated lectin-1 (DCAL-1), a novel, type II, transmembrane, C-type lectin-like protein. DCAL-1 has restricted expression in hemopoietic cells, in particular, DCs and B cells, but T cells and monocytes do not express it. The DCAL-1 locus is within a cluster of C-type lectin-like loci on human chromosome 12p12-13 just 3' to the CD69 locus. The consensus sequence of the DCAL-1 gene was confirmed by RACE-PCR; however, based on sequence alignment with genomic DNA and with various human expressed sequence tags, we predict that DCAL-1 has two splice variants. C-type lectins share a common sequence motif of 14 invariable and 18 highly conserved aa residues known as the carbohydrate recognition domain. DCAL-1, however, is missing three of the cysteine residues required to form the standard carbohydrate recognition domain. DCAL-1 mRNA and protein expression are increased upon the differentiation of monocytes to CD1a(+) DCs. B cells also express high levels of DCAL-1 on their cell surface. Using a DCAL-1 fusion protein we identified a population of CD4(+) CD45RA(+) T cells that express DCAL-1 ligand. Coincubation with soluble DCAL-1 enhanced the proliferation of CD4(+) T cells in response to CD3 ligation and significantly increased IL-4 secretion. In contrast, coincubation with soluble DC-specific ICAM-3-grabbing nonintegrin (CD209) fusion protein as a control had no effect on CD4(+) T cell proliferation or IL-4 and IFN-gamma secretion. Therefore, the function of DCAL-1 on DCs and B cells may act as a T cell costimulatory molecule, which skews CD4(+) T cells toward a Th2 response by enhancing their secretion of IL-4.
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