Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis

In a search for genes expressed by dendritic cells (DC), we have cloned cDN As encoding different forms of an asialoglycoprotein receptor (ASGPR). The DC-ASGPR represents long and short isoforms of human macrophage lectin, a C a2+-dependent type II transmembrane lectin displaying considerable homology with the HI and H2 subunits of the hepatic ASGPR. Immunoprecipitation from DC using an anti-DC-ASGPR mAb yielded a major 40-kDa protein with an isoel ectric point of 8.2. DC-ASGPR mRNA was observed predominantly in immune tis sues. Both isoforms were detected in DC and granulocytes, but not in T, B, or NK cells, or monocytes. DC-ASGPR species were restricted to the CD14-der ived DC obtained from CD34(+) progenitors, while absent from the CD1a-deriv ed subset. Accordingly, both monocyte-derived DC and tonsillar interstitial -type DC expressed DC-ASGPR protein, while Langerhans-type cells did not. F urthermore, DC-ASGPR is a feature of immaturity, as expression was lost upo n CD40 activation. In agreement with the presence of tyrosine-based and dil eucine motifs in the intracytoplasmic domain, mAb against DC-ASGPR was rapi dly internalized by DC at 37 degreesC. Finally, intracellular DC-ASGPR was localized to early endosomes, suggesting that the receptor recycles to the cell surface following internalization of ligand. Our findings identify DC- ASGPR/human macrophage lectin as a feature of immature DC, and as another l ectin important for the specialized Ag-capture function of DC.