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.

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