ASGPR/MGL (asialoglycoprotein / macrophage galactose lectin receptor) / CD301 is a Ca2+ 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 its 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°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. (Valladeau J et al, 2001, J. Immunol., 167: 5767).