K. Ariizumi et al., Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning, J BIOL CHEM, 275(26), 2000, pp. 20157-20167
Dendritic cells (DC) are special subsets of antigen presenting cells charac
terized by their potent capacity to activate immunologically naive T cells.
By subtracting the mRNAs expressed by the mouse epidermus-derived DC line
XS52 with the mRNAs expressed by the J774 macrophage line, we identified fi
ve novel genes that were expressed selectively by this DC line. One of thes
e genes encoded a type II membrane-integrated polypeptide of 244 amino acid
s containing a putative carbohydrate recognition domain motif at the COOH-t
erminal end. This molecule, termed "dectin-1," was expressed abundantly at
both mRNA and protein levels by the XS52 DC line, but not by non-DC lines (
including the J774 macrophage line). Dectin-1 mRNA was detected predominant
ly in spleen and thymus (by Northern blotting) and in skin-resident DC, i.e
. Langerhans cells (by reverse transcription-polymerase chain reaction). Af
finity-purified antibody against dectin-1 identified a 43-kDa glycoprotein
in membrane fractions isolated from the XS52 DC line and from the dectin-1
cDNA-transfected COS-1 cells. His-tagged recombinant proteins containing th
e extracellular domains of dectin-1 showed marked and specific binding to t
he surface of T cells and promoted their proliferation in the presence of a
nti-CD3 monoclonal antibody at suboptimal concentrations. These in vitro re
sults suggest that dectin-1 on DC may bind to as yet undefined ligand(s) on
T cells, thereby delivering T cell co-stimulatory signals. Not only do the
se results document the efficacy of subtractive cDNA cloning for the identi
fication of unique genes expressed by DC, they also provide a framework for
studying the physiological function of dectin-1.