The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family

Eur J Immunol. 1998 Dec;28(12):4071-83. doi: 10.1002/(SICI)1521-4141(199812)28:12<4071::AID-IMMU4071>3.0.CO;2-O.


The human gp200-MR6 molecule has previously been shown to have either an antagonistic or agonistic effect on IL-4 function, demonstrated by inhibition of IL-4-induced proliferation of T cells or mimicking of IL-4-induced maturation of epithelium, respectively. We now show that gp200-MR6 ligation can also mimic IL-4 and have an anti-proliferative pro-maturational influence within the immune system, causing up-regulation of co-stimulatory molecules on B lymphocytes. Biochemical analysis and cDNA cloning reveal that gp200-MR6 belongs to the human macrophage mannose receptor family of multidomain molecules. It comprises 1722 amino acids in toto (mature protein, 1695 amino acids; signal sequence, 27 amino acids) organized into 12 external domains (an N-terminal cysteine-rich domain, a fibronectin type II domain and 10 C-type carbohydrate recognition domains), a transmembrane region and a small cytoplasmic C terminus (31 amino acids) containing a single tyrosine residue (Y1679), but no obvious kinase domain. Strong amino acid sequence identity (77%) suggests that gp200-MR6 is the human homologue of the murine DEC-205, indicating that this molecule has much wider functional activity than its classical endocytic role. We also show that the gp200-MR6 molecule is closely associated with tyrosine kinase activity; the link between gp200-MR6 and the IL-4 receptor may therefore be via intracellular signaling pathways, with multifunctionality residing in its extracellular multidomain structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD*
  • B-Lymphocytes / immunology*
  • Cloning, Molecular
  • Glycoproteins / genetics
  • Glycoproteins / immunology*
  • Humans
  • Interleukin-4 / immunology*
  • Lectins, C-Type*
  • Ligands
  • Lymphocyte Activation*
  • Macrophages / immunology
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Minor Histocompatibility Antigens
  • Molecular Mimicry
  • Molecular Sequence Data
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Interleukin-4 / agonists
  • Receptors, Interleukin-4 / antagonists & inhibitors
  • Receptors, Interleukin-4 / immunology*
  • Sequence Alignment


  • Antigens, CD
  • DEC-205 receptor
  • Glycoproteins
  • Lectins, C-Type
  • Ligands
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • Receptors, Interleukin-4
  • Interleukin-4

Associated data

  • GENBANK/AF064827