The B7 homolog butyrophilin BTN2A1 is a novel ligand for DC-SIGN.
The MHC-encoded butyrophilin, BTN2A1, is a cell surface glycoprotein related to the extended family of B7 costimulatory molecules. BTN2A1 mRNA was expressed in most human tissues, but protein expression was significantly lower in leukocytes. An Ig-fusion protein of BTN2A1 bound to immature monocyte-derived dendritic cells. Binding diminished upon MoDC maturation and no binding was detected to Langerhans cells. Induction of the counterreceptor was IL-4 dependent and occurred early during dendritic cell differentiation. The interaction required the presence of Ca2+ and was mediated by high-mannose oligosaccharides. These properties matched DC-SIGN, a DC-specific HIV-1 entry receptor. This was confirmed by binding of soluble BTN2A1 to DC-SIGN-transfectants and its inhibition by a specific Ab. DC-SIGN bound to native BTN2A1 expressed on a range of tissues. However, BTN2A1 was not recognized on some normal cells such as HUVECs despite a similar expression level. The BTN2A1 of tumor cells such as HEK293T have more high-mannose moieties in comparison to HUVECs, and those high-mannose moieties are instrumental for binding to DC-SIGN. The data are consistent with tumor- or tissue-specific glycosylation of BTN2A1 governing recognition by DC-SIGN on immature monocyte-derived dendritic cells.
Malcherek
Georg
G
Department of Pathology, Division of Immunology, University of Cambridge, Cambridge, United Kingdom. gfjm2@cam.ac.uk
Mayr
Luzia
L
Roda-Navarro
Pedro
P
Rhodes
David
D
Miller
Nigel
N
Trowsdale
John
J
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D000071797:Butyrophilins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007801:Langerhans Cells / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D040681:Structural Homology, Protein; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin