ASGPR/MGL (asialoglycoprotein / macrophage galactose lectin receptor /CD301 is a Ca(2+)-dependent type II transmembrane lectin. Immunoprecipitation from DCs using anti-DC-ASGPR mAb yields a major 40-kDa protein. ASGPR mRNA is observed predominantly in immune tissues (DCs and granulocytes), but not in T, B, or NK cells, or monocytes. ASGPR species are restricted to the CD14-derived DCs obtained from CD34(+) progenitors, while absent from the CD1a-derived subset. Accordingly, both monocyte-derived DCs and tonsillar interstitial-type DCs express ASGPR protein, while Langerhans-type cells do not. ASGPR is a feature of immaturity, as expression is lost upon CD40L activation. In agreement with the presence of tyrosine-based and dileucine motifs in the intracytoplasmic domain, mAb against DC-ASGPR is rapidly internalized by DCs at 37 degrees C. Finally, intracellular ASGPR is localized in early endosomes, suggesting that the receptor recycles to the cell surface following internalization of ligand. ASGPR/HML is a feature of immature DCs and a subtype of macrophages, and likely important for the specialized antigen-capture function of DCs.