Dendritic cell-associated lectin-1: a novel dendritic cell-associated, C-type lectin-like molecule enhances T cell secretion of IL-4.
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.
Ryan
Elizabeth J
EJ
Regional Primate Research Center, Box 357330, University of Washington, Seattle, WA 98195, USA. ejryan@u.washington.edu
Marshall
Aaron J
AJ
Magaletti
Dario
D
Floyd
Helen
H
Draves
Kevin E
KE
Olson
N Eric
NE
Clark
Edward A
EA
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001773:Blood Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; C470184:CLECL1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D015847:Interleukin-4