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 cDNAs encoding different forms of an asialoglycoprotein receptor (ASGPR). The DC-ASGPR represents long and short isoforms of human macrophage lectin, a Ca(2+)-dependent type II transmembrane lectin displaying considerable homology with the H1 and H2 subunits of the hepatic ASGPR. Immunoprecipitation from DC using an anti-DC-ASGPR mAb yielded a major 40-kDa protein with an isoelectric point of 8.2. DC-ASGPR mRNA was observed predominantly in immune tissues. 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-derived DC obtained from CD34(+) progenitors, while absent from the CD1a-derived subset. Accordingly, both monocyte-derived DC and tonsillar interstitial-type DC expressed DC-ASGPR protein, while Langerhans-type cells did not. Furthermore, DC-ASGPR is a feature of immaturity, as expression was lost upon CD40 activation. In agreement with the presence of tyrosine-based and dileucine motifs in the intracytoplasmic domain, mAb against DC-ASGPR was rapidly internalized by DC at 37 degrees C. 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 lectin important for the specialized Ag-capture function of DC.
Valladeau
J
J
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Duvert-Frances
V
V
Pin
J J
JJ
Kleijmeer
M J
MJ
Ait-Yahia
S
S
Ravel
O
O
Vincent
C
C
Vega
F
F
Helms
A
A
Gorman
D
D
Zurawski
S M
SM
Zurawski
G
G
Ford
J
J
Saeland
S
S
D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000235:genetics; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D010802:Phylogeny; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000276:immunology
D037263:Asialoglycoprotein Receptor; D019013:CD40 Antigens; C113583:Clecsf8 protein, mouse; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface