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.
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.
McKay
P F
PF
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, GB.
Imami
N
N
Johns
M
M
Taylor-Fishwick
D A
DA
Sedibane
L M
LM
Totty
N F
NF
Hsuan
J J
JJ
Palmer
D B
DB
George
A J
AJ
Foxwell
B M
BM
Ritter
M A
MA
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D015778:Minor Histocompatibility Antigens; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D016415:Sequence Alignment
D015703:Antigens, CD; C093569:DEC-205 receptor; D006023:Glycoproteins; D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D019948:Receptors, Interleukin-4; D015847:Interleukin-4